Affinage

ANO1

Anoctamin-1 · UniProt Q5XXA6

Length
986 aa
Mass
114.1 kDa
Annotated
2026-06-09
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANO1 (TMEM16A) is the molecular basis of native Ca2+-activated chloride channel (CaCC) currents and serves as a Ca2+- and voltage-gated anion channel whose activity drives epithelial secretion, smooth muscle and pacemaker excitability, neuronal firing, and developmental morphogenesis (PMID:18724360, PMID:19965375). Channel gating is tuned at multiple levels: the Ca2+/calmodulin complex dynamically sets the HCO3-/Cl- permeability ratio (PMID:23248295), CaMKII phosphorylation at S528 promotes current rundown (reversed by PP1/PP2A) (PMID:31461344), and sustained activity depends on membrane PI(4,5)P2 with additional modulation by cholesterol and fatty acids (PMID:29277655). ANO1 is preferentially activated by spatially restricted Ca2+ signals from intracellular release sites rather than bulk cytosolic Ca2+ (PMID:25398532), a logic embodied in defined membrane signaling units — a stable ANO1–CaV1.2–IP3R complex underlying EC-coupling and myogenic tone in arterial smooth muscle (PMID:37702787), coupling to stretch-activated cation channels in cerebral arteries (PMID:22872152), and functional partnership with TRPV4 in gland acinar cells and TRPV3 in keratinocytes that channels store-derived Ca2+ into ANO1-mediated Cl- currents (PMID:29187363, PMID:36690845). Through these mechanisms ANO1 mediates exocrine Cl-/HCO3- secretion and saliva production (PMID:18724360, PMID:27510033), airway and intestinal mucus secretion (PMID:30586313), pacemaker slow-wave activity in interstitial cells of Cajal (PMID:19965375), pressure-induced vasoconstriction and ischemic pericyte/capillary constriction via a Cl- efflux–depolarization–VGCC amplification loop (PMID:22872152, PMID:35316222), medial habenula cholinergic neuron excitability controlling anxiety behavior (PMID:31782602), and BDNF-driven radial glial process extension during cortical development (PMID:31147466). ANO1 is also required for CFTR membrane expression and cAMP-activated Cl- secretion through compartmentalized signalosomes containing ADCY1 and EPAC1 (PMID:28963502, PMID:29331508). In cancer, ANO1 promotes proliferation and survival by driving ERK1/2/cyclin D1 signaling and suppressing Bim (PMID:22564524, PMID:25541940, PMID:28899969) and drives migration/metastasis via an EGFR/STAT3/ROCK1 feedback loop with moesin phosphorylation (PMID:34603794); it physically associates with EGFR through the EGFR juxtamembrane domain in a reciprocally stabilizing complex (PMID:25823819). Beyond its channel role, ANO1 performs non-conducting scaffolding functions: in hepatocytes it binds VAMP3 to trigger its degradation and impair GLUT2 trafficking (PMID:32440483) and binds GPX4 to induce its ubiquitination and promote ferroptosis (PMID:36572666). Rare gain-of-function ANO1 variants with increased Ca2+ sensitivity predispose to moyamoya disease (PMID:37253099).

Mechanistic history

Synthesis pass · year-by-year structured walk · 34 steps
  1. 2008 High

    Established the molecular identity of the long-sought calcium-activated chloride channel by showing TMEM16A reconstitutes native CaCC currents and is required for them in vivo.

    Evidence Heterologous expression with whole-cell patch clamp plus RNAi knockdown in mice with saliva readout

    PMID:18724360

    Open questions at the time
    • Did not resolve stoichiometry or the structural basis of Ca2+ gating
    • Channel pore architecture not defined
  2. 2009 High

    Mapped ANO1 to apical epithelial membranes and to interstitial cells of Cajal, defining it as the pacemaker CaCC driving rhythmic gut contraction.

    Evidence KO-validated antibody immunolocalization and knockout-mouse gastric contractility assay

    PMID:19965375

    Open questions at the time
    • Did not establish how ICC slow-wave Ca2+ signals are generated upstream
    • Cell-type specificity of pacemaker function not fully dissected
  3. 2012 High

    Showed that ANO1 anion selectivity is not fixed but dynamically set by Ca2+/calmodulin, explaining tunable HCO3- versus Cl- permeability.

    Evidence Excised-patch electrophysiology with recombinant calmodulin in HEK293T and native acinar cells

    PMID:23248295

    Open questions at the time
    • CaM binding site on ANO1 not structurally defined
    • Physiological contexts where selectivity switches occur not enumerated
  4. 2012 High

    Defined ANO1 as the effector of the myogenic response in cerebral arteries, activated by stretch via local cation-channel Ca2+ rather than L-type channels or store release.

    Evidence RNAi knockdown, inhibitory antibodies, cell-attached patch clamp, pressure myography

    PMID:22872152

    Open questions at the time
    • Identity of the stretch-activated cation channel not established
    • Molecular coupling between cation channel and ANO1 unresolved
  5. 2012 Medium

    Linked ANO1 overexpression to tumor growth through ERK1/2 activation and cyclin D1 induction, opening its oncogenic MAPK axis.

    Evidence Gain/loss-of-function in HNSCC lines, xenografts, MEK/ERK inhibitors and dominant-negative ERK1/2

    PMID:22564524

    Open questions at the time
    • Whether channel conductance versus scaffolding drives ERK activation unresolved
    • Single-lab observation
  6. 2013 Medium

    Showed DOG1/ANO1 oncogenic effect in GIST operates through the tumor microenvironment (IGFBP5/IGF axis) rather than direct cell-autonomous growth or KIT signaling.

    Evidence RNAi and inhibitor treatment in GIST xenografts with expression profiling

    PMID:23576565

    Open questions at the time
    • Mechanism linking ANO1 to IGFBP5 regulation unknown
    • In vitro growth effect explicitly negative, leaving channel role unclear
  7. 2014 Medium

    Connected ANO1 to G1/S cell-cycle progression and Rb phosphorylation, providing a proliferation mechanism in ICC and cancer cells.

    Evidence Ano1 KO mice, EdU/Ki67, low-Cl- media and Cl- channel blockers with KO controls

    PMID:21940901

    Open questions at the time
    • Signal linking Cl- conductance to Rb phosphorylation unresolved
    • Cl- channel blocker specificity a caveat
  8. 2014 Medium

    Identified ANO1 as a primary ciliogenesis factor localized to a pre-ciliary 'nimbus' with Cdc42, Arl13b and exocyst Sec6.

    Evidence Immunofluorescence, shRNA knockdown, pharmacological inhibition, confocal microscopy

    PMID:24694595

    Open questions at the time
    • Whether ANO1 channel activity is required for ciliogenesis unclear
    • Functional interaction with exocyst not biochemically defined
  9. 2014 Medium

    Established ANO1 as a phenotypic switch in HNSCC ('grow or go'), with S970 required for EMT and Radixin association but dispensable for proliferation.

    Evidence Proteomic screen, S970A mutant, Radixin co-IP, orthotopic metastasis model, bisulfite sequencing

    PMID:24919570

    Open questions at the time
    • How S970 phosphorylation state is controlled unknown
    • Structural basis of Radixin binding not defined
  10. 2014 Medium

    Extended the ERK/cyclin D1 oncogenic mechanism to colorectal cancer, linking ANO1 loss to MEK/ERK suppression and G1/S arrest.

    Evidence shRNA knockdown with migration/invasion assays and MAPK Western blots

    PMID:25541940

    Open questions at the time
    • Single knockdown approach
    • Upstream link from ANO1 to MEK not established
  11. 2014 Medium

    Reframed ANO1 gating around localized ER store Ca2+ rather than bulk cytosolic Ca2+, establishing microdomain signaling logic.

    Evidence Co-localization imaging and electrophysiology synthesized across cell types

    PMID:25398532

    Open questions at the time
    • Synthesis review rather than single reconstitution
    • Molecular tethering to IP3R sites not yet defined
  12. 2015 High

    Showed PKCα mediates purinergic activation of ANO1 Cl- secretion in biliary epithelium, adding a kinase regulatory input.

    Evidence Patch clamp with recombinant PKCα dialysis, PKCα and TMEM16A siRNA

    PMID:26542395

    Open questions at the time
    • PKCα phosphorylation site on ANO1 not identified
    • Direct versus indirect phosphorylation not distinguished
  13. 2015 Medium

    Linked angiotensin-II-induced ANO1 upregulation to VSMC proliferation and hypertension development in vivo.

    Evidence SHR model, siRNA, T16Ainh-A01, primary VSMC culture, blood pressure measurement

    PMID:25739000

    Open questions at the time
    • Transcriptional pathway from AngII to ANO1 not defined
    • Single lab
  14. 2016 Medium

    Demonstrated ANO1 transports HCO3- into the pancreatic acinar lumen, buffering luminal pH after zymogen exocytosis.

    Evidence Intraluminal pH measurement in isolated acini with T16inh-A01

    PMID:27510033

    Open questions at the time
    • Contribution relative to other transporters not quantified
    • Pharmacological inhibitor only
  15. 2017 High

    Established a surprising codependence of CFTR on ANO1, showing ANO1 is required for CFTR membrane expression, cAMP-activated currents, and ER Ca2+ store release.

    Evidence Two tissue-specific Cre-lox KO lines, Ussing chamber, patch clamp, CFTR surface biotinylation

    PMID:28963502

    Open questions at the time
    • Molecular mechanism of CFTR trafficking dependence unresolved
    • Mechanism of SOcAMPS engagement not detailed
  16. 2017 Medium

    Defined the compartmentalized signalosome (GPCR-ADCY1-EPAC1) coordinating ANO1 and CFTR, and showed Golgi-independent ANO1 maturation.

    Evidence GPCR knockdown, ADCY1/EPAC1 localization, patch clamp, Ussing chamber

    PMID:29331508

    Open questions at the time
    • Physical scaffold organizing the signalosome not identified
    • Golgi-independent trafficking route undefined
  17. 2017 Medium

    Showed ANO1 promotes cancer survival by suppressing Bim downstream of ERK1/2, an anti-apoptotic mechanism complementing its proliferative role.

    Evidence siRNA, viability/apoptosis assays, xenograft, human HNSCC tissue analysis

    PMID:28899969

    Open questions at the time
    • Direct link between ANO1 conductance and ERK/Bim not mechanistically resolved
    • Single lab
  18. 2017 High

    Defined PI(4,5)P2 as a required cofactor preventing channel rundown and lipid/cholesterol/fatty-acid modulation of ANO1 gating.

    Evidence Inside-out and whole-cell patch clamp with PI(4,5)P2 depletion/supplementation, cholesterol and fatty acid manipulation

    PMID:29277655

    Open questions at the time
    • PI(4,5)P2 binding site not structurally mapped
    • Physiological lipid concentrations governing gating not defined
  19. 2017 Medium

    Linked ANO1 to VRAC component LRRC8A and to Ca2+-triggered exocytosis, hinting at roles beyond Cl- conductance.

    Evidence Co-IP, LRRC8A siRNA, patch clamp, membrane capacitance and FM4-64 imaging

    PMID:27514381

    Open questions at the time
    • Functional significance of ANO1-LRRC8A interaction unclear
    • Whether ANO1 directly mediates exocytosis not established
  20. 2018 High

    Established ANO1 as essential for basal ATP-driven mucus secretion in airway and intestine, while showing cholinergic compound exocytosis is ANO1-independent.

    Evidence Two tissue-specific KO lines, inhibitors, siRNA, mucus secretion assays

    PMID:30586313

    Open questions at the time
    • Mechanism coupling ANO1 to mucus granule release not defined
    • Relationship to the CFTR codependence not integrated
  21. 2018 Medium

    Showed TRPV4 functionally feeds ANO1 in gland acinar cells via IP3-dependent Ca2+, contributing to muscarinic and temperature-dependent secretion.

    Evidence TRPV4 KO mice, TRPV4 agonist/antagonist, patch clamp in acinar cells

    PMID:29187363

    Open questions at the time
    • Physical TRPV4-ANO1 proximity not established
    • Single lab
  22. 2019 High

    Identified ANO1 as required for cholinergic neuron firing in the medial habenula, linking channel function to anxiety and social behavior.

    Evidence Conditional KO, RNAscope, patch clamp, DREADD inhibition, behavioral assays

    PMID:31782602

    Open questions at the time
    • Mechanism by which ANO1 shapes afterhyperpolarization not detailed
    • Upstream Ca2+ source in mHb neurons not defined
  23. 2019 High

    Showed ANO1 mediates BDNF-driven radial glial process extension required for proper cortical lamination, defining a developmental role.

    Evidence Ano1 KO mice, cortical layer analysis, knockdown/overexpression, patch clamp, BDNF stimulation

    PMID:31147466

    Open questions at the time
    • Link from BDNF receptor signaling to ANO1 activation not resolved
    • How Cl- flux drives process extension unclear
  24. 2019 High

    Identified CaMKII phosphorylation at S528 as a driver of channel rundown counteracted by PP1/PP2A, defining phospho-regulation of gating.

    Evidence Patch clamp in HEK293, CaMKII and phosphatase inhibitors, S528A mutation, ATP-free pipette

    PMID:31461344

    Open questions at the time
    • Physiological triggers of CaMKII-mediated rundown not defined
    • Whether S528 phosphorylation alters Ca2+ sensitivity directly unclear
  25. 2019 Medium

    Identified the transcriptional/epigenetic basis of ANO1 upregulation in gastric cancer via SP1-recruited MLL1 and H3K4me3 at the promoter.

    Evidence ChIP for SP1 and MLL1, H3K4me3 analysis, promoter luciferase, SP1 perturbation

    PMID:30871776

    Open questions at the time
    • Whether this axis operates in other cancers untested
    • Single lab
  26. 2020 High

    Revealed a non-channel scaffolding function: hepatocyte ANO1 binds and degrades VAMP3, disrupting SNARE complexes and GLUT2 trafficking to drive NAFLD.

    Evidence Hepatocyte-specific KO and transgenic mice, co-IP, SNARE analysis, GLUT2 biotinylation, VAMP3 rescue

    PMID:32440483

    Open questions at the time
    • Mechanism by which ANO1 induces VAMP3 degradation not detailed
    • Whether channel activity contributes unresolved
  27. 2021 Medium

    Defined an EGFR/STAT3/ROCK1 positive-feedback loop in which ANO1 drives metastasis and ROCK1 reciprocally enhances ANO1 via moesin T558 phosphorylation.

    Evidence Migration/invasion assays, patch clamp, ROCK1/RhoA overexpression, moesin phospho-Western, lung metastasis model

    PMID:34603794

    Open questions at the time
    • Direct phosphorylation site on ANO1 by ROCK1 not mapped
    • Single lab
  28. 2021 Medium

    Showed ANO1 is the CaCC in type I taste cells, activated by ATP via P2Y receptors, integrating it into taste signaling.

    Evidence Immunohistochemistry, patch clamp in isolated taste cells, ion substitution, Ani-9 blockade

    PMID:34089532

    Open questions at the time
    • Functional role of type I cell Cl- currents in taste perception unclear
    • Single lab
  29. 2022 High

    Defined a pericyte Cl- efflux–depolarization–VGCC amplification loop by which ANO1 worsens ischemic capillary constriction and pericyte death.

    Evidence Inhibitors, rodent stroke model, two-photon Ca2+/diameter imaging, patient genetics

    PMID:35316222

    Open questions at the time
    • Initial Ca2+ trigger in ischemic pericytes not defined
    • Translational relevance of patient genetic association limited
  30. 2022 High

    Revealed a second scaffolding function: ANO1 binds GPX4 to induce its ubiquitination, promoting ferroptosis in hepatic ischemia/reperfusion injury.

    Evidence Hepatocyte-specific KO/overexpression mice, co-IP, ubiquitination assays, ferroptosis modulators, interaction-disruption rescue

    PMID:36572666

    Open questions at the time
    • E3 ligase mediating GPX4 ubiquitination not identified
    • Apparent opposite ferroptosis role in cancer not reconciled
  31. 2022 Medium

    Linked ANO1 to chemoresistance via ROS/TRPML1/β-catenin-MITF-driven lysosomal exocytosis that expels cisplatin from SCCHN cells.

    Evidence Genetic/pharmacological lysosome inhibition, ROS and pathway analysis, cisplatin quantification, PDX model

    PMID:35286200

    Open questions at the time
    • How ANO1 initiates lysosomal biogenesis signaling unclear
    • Single lab
  32. 2023 High

    Resolved a stable ANO1-CaV1.2-IP3R signaling complex as the molecular EC-coupling unit driving Ca2+ waves and tone in pulmonary arterial smooth muscle.

    Evidence Smooth-muscle-specific KO, co-IP, super-resolution nanomicroscopy, GCaMP imaging, pressure myography

    PMID:37702787

    Open questions at the time
    • Stoichiometry and structural arrangement of the complex unknown
    • Whether complex composition varies across vascular beds unclear
  33. 2023 Medium

    Showed ANO1 promotes immunotherapy resistance by inhibiting ferroptosis via PI3K-Akt and recruiting CAFs through TGF-β, remodeling the tumor microenvironment.

    Evidence Knockdown/inhibition in GI cancer lines, CDX/PDX models, multi-omics, CD8+ T-cell assays

    PMID:37341301

    Open questions at the time
    • Direct molecular link from ANO1 to PI3K-Akt not defined
    • Channel versus scaffolding contribution unresolved
  34. 2023 Medium

    Connected ANO1 to human disease by identifying rare gain-of-function variants with increased Ca2+ sensitivity that predispose to moyamoya disease.

    Evidence Exome sequencing, family segregation (LOD 3.3), patch clamp of variants in heterologous cells

    PMID:37253099

    Open questions at the time
    • Functional validation across the full variant set limited
    • Tissue mechanism linking gain-of-function to cerebrovascular pathology undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ANO1's channel-conducting role is mechanistically distinguished from its non-conducting scaffolding functions (VAMP3/GPX4 degradation, EGFR/Radixin/LRRC8A complexes) within the same protein remains unresolved.
  • No structure-function separation of channel versus scaffold domains across contexts
  • Opposing ferroptosis roles in liver versus cancer not reconciled
  • Tissue-specific partner selection not explained

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0060090 molecular adaptor activity 3 GO:0140299 molecular sensor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005764 lysosome 1 GO:0005929 cilium 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-1640170 Cell Cycle 2 R-HSA-382551 Transport of small molecules 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1266738 Developmental Biology 1
Partners
CALM1 (CALMODULIN)CAV1.2 (CACNA1C)CFTREGFRGPX4ITPR/IP3RLRRC8AVAMP3
Complex memberships
ANO1-CFTR/ADCY1/EPAC1 signalosomeANO1-CaV1.2-IP3R EC-coupling complexANO1-EGFR complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 TMEM16A (ANO1) is a calcium-activated chloride channel: heterologous expression produces Ca2+-activated Cl- currents with biophysical and pharmacological properties matching native CaCC currents; knockdown of mouse Ano1 markedly reduced native Ca2+-activated chloride currents and saliva production in mice. Heterologous expression, whole-cell patch clamp, RNAi knockdown in mice with functional readout (saliva production) Nature High 18724360
2009 TMEM16A localizes to apical membranes of epithelial cells in exocrine glands and trachea, to airway and reproductive-tract smooth muscle cells, and to interstitial cells of Cajal (ICC) in the GI tract (but not GI smooth muscle); TMEM16A knockout mice show diminished rhythmic gastric smooth muscle contraction, establishing its role as the pacemaker CaCC in ICC. TMEM16A-specific antibody validated in knockout mice (immunofluorescence, Western blot), knockout mouse contractility assay Proceedings of the National Academy of Sciences of the United States of America High 19965375
2012 The anion selectivity (HCO3-/Cl- permeability ratio) of ANO1 is dynamically regulated by the Ca2+/calmodulin complex: calmodulin physically interacts with ANO1 in a [Ca2+]i-dependent manner, and addition of recombinant calmodulin to the cytosolic side of excised patches reversibly increased PHCO3/PCl. Whole-cell and excised-patch electrophysiology in HEK293T cells; recombinant calmodulin application; native submandibular gland acinar cells Proceedings of the National Academy of Sciences of the United States of America High 23248295
2012 ANO1/TMEM16A channels in arterial myocytes are activated by membrane stretch (cell swelling/pressure) via a local Ca2+ signal generated by nonselective cation channels (blocked by Gd3+ and SKF-96365, but not by L-type Ca2+ channel blocker nimodipine or store-depletion with thapsigargin); TMEM16A knockdown reduced pressure-induced membrane depolarization and vasoconstriction (myogenic response) without altering K+-induced constriction. RNAi-mediated TMEM16A knockdown, inhibitory antibodies, cell-attached patch clamp, pressure myography in cerebral arteries Circulation research High 22872152
2012 TMEM16A overexpression promotes tumor growth via activation of ERK1/2 and induction of cyclin D1 (MAPK pathway); pharmacologic MEK/ERK inhibition and dominant-negative ERK1/2 constructs abrogated the TMEM16A-mediated growth effect. Stable overexpression and siRNA knockdown in HNSCC cell lines; in vivo xenograft; MEK/ERK inhibitors; dominant-negative ERK1/2; Western blot for p-ERK, cyclin D1 Cancer research Medium 22564524
2014 ANO1/TMEM16A interacts with EGFR via the EGFR trans/juxtamembrane domain; ANO1 expression affects EGFR protein stability, while EGFR signaling elevates ANO1 protein levels, establishing a reciprocal functional and regulatory complex that jointly controls HNSCC cell proliferation. Unbiased proteomics screen, structural EGFR and ANO1 mutant analysis, co-immunoprecipitation, Western blot Oncotarget Medium 25823819
2014 ANO1/TMEM16A is localized in the primary cilium before and during ciliogenesis; before ciliogenesis, ANO1 organizes into a torus-shaped 'nimbus' structure co-enriched with Cdc42, Arl13b, and exocyst component Sec6; pharmacological block or shRNA knockdown of ANO1 interferes with primary ciliogenesis. Immunofluorescence, shRNA knockdown, pharmacological inhibition, confocal microscopy Molecular biology of the cell Medium 24694595
2014 ANO1 regulates cell cycle progression at the G1/S transition: Cl- channel blockers decreased proliferation of ICC and CFPAC-1 cells expressing ANO1, with reduced effect in Ano1-/- cultures; Ano1 knockout mice show fewer proliferating ICC and less phosphorylated retinoblastoma protein. Ano1 knockout mice, Ki67 immunoreactivity, EdU incorporation, cell-cycle analysis, low-Cl- media experiments, Cl- channel blockers American journal of physiology. Gastrointestinal and liver physiology Medium 21940901
2013 DOG1/ANO1 silencing in GIST xenografts delays tumor growth in vivo and upregulates IGFBP5 (an antiangiogenic factor) in explanted tumors; DOG1 silencing or pharmacologic inhibition did not alter cell growth or KIT signaling in vitro, indicating the oncogenic role of DOG1 involves modulation of the IGF/IGFR axis in the tumor microenvironment. RNAi knockdown, DOG1 inhibitor treatment, GIST xenografts, expression profiling, IGFBP5 mRNA quantification Cancer research Medium 23576565
2014 TMEM16A depletion in colorectal cancer SW620 cells suppresses growth, migration, and invasion; mechanistically, TMEM16A knockdown reduces phospho-MEK, phospho-ERK1/2, and cyclin D1 and causes G1/S cell-cycle arrest. shRNA knockdown, MTT, wound-healing, transwell assays, flow cytometry, Western blot for MAPK pathway components PloS one Medium 25541940
2014 ANO1 channel activity is coupled to localized Ca2+ signals from intracellular Ca2+ store release sites (IP3R); in multiple cell types, ANO1 preferentially co-localizes with Ca2+ release sites of the ER rather than responding to bulk cytoplasmic Ca2+. Co-localization imaging, electrophysiology showing differential activation by local vs. global Ca2+ signals (reviewed/synthesized from multiple primary studies) The Journal of physiology Medium 25398532
2015 PKCα regulates TMEM16A-mediated Cl- secretion in biliary epithelial cells: extracellular ATP triggers PKCα translocation to the plasma membrane; intracellular dialysis with recombinant PKCα activates Cl- currents with TMEM16A biophysical properties in control cells but not after TMEM16A siRNA knockdown. Whole-cell patch clamp, recombinant PKCα intracellular dialysis, PKCα siRNA and pharmacologic inhibition, TMEM16A siRNA American journal of physiology. Gastrointestinal and liver physiology High 26542395
2015 ANO1 overexpression in spontaneously hypertensive rats (SHRs) contributes to hypertension; angiotensin II upregulates ANO1 expression in vascular smooth muscle cells (VSMCs), and ANO1 protein level and activity positively correlate with VSMC proliferation; siRNA knockdown of ANO1 prevented hypertensive development. SHR model, siRNA knockdown, ANO1 inhibitor (T16Ainh-A01), angiotensin II stimulation of primary VSMCs, Western blot, blood pressure measurement Journal of molecular and cellular cardiology Medium 25739000
2015 TMEM16A expression shifts HNSCC cells between proliferative and metastatic phenotypes ('grow or go'); S970 residue of TMEM16A is required for effects on cell size and epithelial-to-mesenchymal transition (EMT), and mediates association with Radixin (an actin-scaffolding protein implicated in EMT); S970A mutation does not disrupt TMEM16A-driven proliferation; promoter methylation mediates TMEM16A downregulation during EMT transition. Proteomic screens, stable TMEM16A knockdown, orthotopic mouse metastasis model, S970A point mutation, co-immunoprecipitation with Radixin, bisulfite sequencing, patient tissue analysis Clinical cancer research Medium 24919570
2017 Tissue-specific TMEM16A knockout in mouse intestine and airways not only eliminates Ca2+-activated Cl- currents but also abrogates CFTR-mediated Cl- secretion and cAMP-activated currents; mechanistically, TMEM16A is required for ER Ca2+ store release (engaging SOcAMPS) and for proper membrane expression of CFTR. Tissue-specific Cre-lox KO mice (TMEM16Aflox/flox × FoxJ1-Cre, Vil1-Cre), Ussing chamber, whole-cell patch clamp, surface biotinylation for CFTR membrane expression Scientific reports High 28963502
2017 TMEM16A and CFTR functional coupling in airway epithelial cells is mediated by a compartmentalized signalosome: GPCRs recruit Ca2+-sensitive adenylyl cyclase type 1 (ADCY1) and EPAC1 to membrane domains containing GPCRs, CFTR, and TMEM16A, producing compartmentalized Ca2+ and cAMP signals; maturation and membrane trafficking of TMEM16A can occur independently of the Golgi. GPCR knockdown, ADCY1 and EPAC1 localization studies, Western blot, patch clamp, Ussing chamber Cellular signalling Medium 29331508
2017 TMEM16A is regulated by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2): depletion of PI(4,5)P2 causes Ca2+-dependent current decline; supplying PI(4,5)P2 to inside-out patches attenuates channel rundown; cholesterol modulates TMEM16A activity through both PI(4,5)P2-dependent and -independent mechanisms; fatty acids (stearic, arachidonic, oleic, DHA, EPA) and phosphatidylserine inhibit TMEM16A in a dose- and voltage-dependent manner via membrane-delimited protein-lipid interaction. Patch clamp (whole-cell and inside-out), PI(4,5)P2 depletion (rapamycin system), methyl-β-cyclodextrin cholesterol manipulation, fatty acid application, surface biotinylation Biochimica et biophysica acta. Molecular and cell biology of lipids High 29277655
2017 TMEM16A/ANO1 promotes tumor cell survival by inhibiting apoptosis via downregulation of Bim expression; TMEM16A expression correlates with increased ERK1/2 activity and reduced Bim in human HNSCC. siRNA knockdown, in vitro viability/apoptosis assays, in vivo xenograft, Western blot (Bim, p-ERK1/2), human HNSCC tissue analysis Clinical cancer research Medium 28899969
2017 TMEM16A and LRRC8A (VRAC) can be co-immunoprecipitated; loss of LRRC8A attenuates Ca2+-activated Cl- currents and ANO1-dependent membrane capacitance changes; ANO1-expressing cells show increased membrane capacitance and FM4-64 membrane binding upon intracellular Ca2+ elevation, suggesting a role for ANO1 in exocytosis. Co-immunoprecipitation, LRRC8A siRNA knockdown, patch clamp, membrane capacitance measurements, FM4-64 fluorescence Pflugers Archiv : European journal of physiology Medium 27514381
2018 TMEM16A is essential for basal (ATP-driven) mucus secretion in airways and intestine: ciliated-cell-specific and intestinal-epithelial-specific TMEM16A knockout mice show mucus accumulation in airway club cells and intestinal goblet cells; acute ATP-induced mucus secretion is abrogated by TMEM16A KO in ciliated cells; cholinergic mucus secretion by compound exocytosis is independent of TMEM16A. Tissue-specific KO mice (TMEM16Aflox/flox × FoxJ1-Cre, Vil1-Cre), TMEM16A inhibitors, siRNA knockdown, mucus secretion assays, IL-8 measurement FASEB journal High 30586313
2016 ANO1/TMEM16A transports HCO3- into pancreatic acinar cell lumen under physiological CCK stimulation; T16inh-A01 blockade significantly increases luminal acidification after zymogen granule exocytosis; in acute pancreatitis model, ANO1 acts to attenuate luminal pH shifts. Freshly isolated pancreatic acini with preserved luminal structure, intraluminal pH measurement (fluorescent indicator), specific TMEM16A inhibitor T16inh-A01 The Journal of biological chemistry Medium 27510033
2019 TMEM16A expression in medial habenula (mHb) cholinergic neurons is required for normal action potential firing: conditional knockout of TMEM16A in mHb cholinergic neurons reduces after-hyperpolarization slope and firing frequency, decreases activity of the interpeduncular nucleus, and produces anxiety-related behaviors and deficits in social interaction. Conditional knockout mice (cKO), RNAscope in situ hybridization, immunohistochemistry, whole-cell patch clamp electrophysiology, DREADD chemogenetic inhibition, behavioral assays EMBO reports High 31782602
2019 ANO1/TMEM16A regulates process extension of radial glial cells (RGCs) in the developing brain: ANO1 is expressed and functionally active in RGCs; knockdown suppresses process extension while overexpression stimulates it; BDNF activates ANO1 which is required for BDNF-induced process extension; Ano1-deficient mice show disrupted cortical layers and reduced cortical thickness. Ano1 knockout mice, cortical layer analysis, shRNA knockdown, ANO1 overexpression, patch-clamp electrophysiology in RGCs, BDNF stimulation assays Proceedings of the National Academy of Sciences of the United States of America High 31147466
2019 CaMKII phosphorylates TMEM16A, specifically at serine 528, to promote channel rundown; mutation of S528A attenuates TMEM16A rundown similarly to CaMKII inhibitors; PP1/PP2A phosphatases counteract this effect. ATP-dependent CaMKII activity drives current decay. Whole-cell patch clamp in HEK293 cells expressing mouse TMEM16A; CaMKII inhibitors (AIP, KN-93); PP1/PP2A inhibitors (okadaic acid, cantharidin); S528A point mutation; ATP-free pipette solutions American journal of physiology. Cell physiology High 31461344
2021 TMEM16A activation promotes breast cancer cell migration and invasion; mechanistically, TMEM16A activates EGFR/STAT3/ROCK1 signaling, and ROCK1 in turn enhances TMEM16A channel activity via phosphorylation of moesin at T558, creating a positive feedback loop. Wound-healing and transwell assays, whole-cell patch clamp, ROCK1/RhoA overexpression, moesin T558 phosphorylation Western blot, mouse lung metastasis model Journal of advanced research Medium 34603794
2022 Pericyte TMEM16A amplifies capillary constriction after ischemia: a small rise in [Ca2+]i activates TMEM16A-dependent Cl- efflux, depolarizing pericytes and opening voltage-gated Ca2+ channels to amplify [Ca2+]i further; TMEM16A inhibition slows ischemia-evoked pericyte [Ca2+]i rise, capillary constriction, and pericyte death in a rodent stroke model. TMEM16A inhibitors, rodent stroke model, live two-photon imaging of [Ca2+]i and capillary diameter, genetic analysis of TMEM16A expression in patient stroke recovery The Journal of clinical investigation High 35316222
2022 TMEM16A interacts with GPX4 to induce GPX4 ubiquitination and degradation, thereby enhancing ferroptosis in hepatocytes; disruption of the TMEM16A-GPX4 interaction abrogates GPX4 ubiquitination, ferroptosis, and hepatic ischemia/reperfusion injury; hepatocyte-specific TMEM16A KO reduces I/R injury in mice. Hepatocyte-specific TMEM16A KO and overexpression transgenic mice, co-immunoprecipitation, ubiquitination assays, ferroptosis inducers/inhibitors, in vitro hypoxia/reoxygenation model Cell death & disease High 36572666
2022 TMEM16A overexpression promotes lysosomal biogenesis and exocytosis via a pathway requiring ROS, TRPML1, and β-catenin–MITF signaling, enabling expulsion of intracellular cisplatin and contributing to cisplatin resistance in SCCHN. Genetic and pharmacological (hydroxychloroquine) lysosomal inhibition, ROS measurement, TRPML1 and β-catenin pathway analysis, cisplatin quantification, murine SCCHN PDX model Proceedings of the National Academy of Sciences of the United States of America Medium 35286200
2020 Hepatocyte TMEM16A interacts with VAMP3 to induce VAMP3 degradation, suppressing VAMP3/syntaxin 4 and VAMP3/SNAP23 SNARE complexes; this impairs GLUT2 translocation to the plasma membrane and hepatic glucose uptake, contributing to NAFLD; VAMP3 overexpression reverses TMEM16A-induced metabolic dysfunction. Hepatocyte-specific TMEM16A KO and transgenic mice, co-immunoprecipitation, VAMP3/syntaxin4/SNAP23 complex analysis, GLUT2 surface biotinylation, glucose uptake assays, VAMP3 overexpression/knockdown rescue experiments Advanced science High 32440483
2018 TRPV4 functionally interacts with ANO1 in salivary and lacrimal gland acinar cells: TRPV4 activation increases [Ca2+]i via an IP3-dependent mechanism and evokes ANO1-mediated chloride currents and acinar cell shrinkage; TRPV4-deficient mice and TRPV4 antagonist treatment reduce muscarinic salivation and lacrimation; temperature dependence of muscarinic salivation depends mainly on TRPV4. Patch clamp, TRPV4 knockout mice, TRPV4-specific activator (GSK1016790A) and antagonist (HC-067047), isolated acinar cells from salivary and lacrimal glands FASEB journal Medium 29187363
2023 ANO1, CaV1.2, and IP3R form a stable localized signaling complex in pulmonary arterial smooth muscle cell plasma membrane: co-immunoprecipitation with anti-ANO1 antibody pulls down both CaV1.2 and IP3R; co-assembly confirmed by confocal and superresolution nanomicroscopy; smooth muscle-specific ANO1 ablation equally abolishes 5-HT-induced Ca2+ waves and tone as CaV1.2 or IP3R inhibition. Smooth muscle-specific ANO1 KO, co-immunoprecipitation, confocal and superresolution nanomicroscopy, pharmacological inhibition of ANO1/CaV1.2/IP3R, GCaMP3/6 Ca2+ imaging, pressure myography The Journal of general physiology High 37702787
2023 ANO1 inhibits cancer ferroptosis through PI3K-Akt signaling and promotes TGF-β release to recruit cancer-associated fibroblasts, thereby remodeling the tumor immune microenvironment and generating resistance to anti-PD-1 immunotherapy; ANO1 knockdown or inhibition enhances immunotherapeutic effectiveness. ANO1 knockdown and inhibition in multiple GI cancer cell lines, CDX and PDX mouse models, multi-omics study, TGF-β and PI3K-Akt pathway analysis, CD8+ T cell activity assays Advanced science Medium 37341301
2023 Rare gain-of-function variants in ANO1 (including p.Met658Val) predispose to moyamoya disease; patch-clamp recordings of these variants show increased sensitivity to intracellular Ca2+. Exome sequencing, family-based segregation analysis (LOD score 3.3), patch-clamp electrophysiology of ANO1 variants in heterologous expression Brain Medium 37253099
2019 SP1 transcription factor increases ANO1 transcription in gastric cancer by recruiting MLL1 to the ANO1 promoter region, facilitating H3K4 trimethylation and subsequently promoting ANO1 expression. ChIP for SP1 and MLL1 at ANO1 promoter, H3K4me3 Western blot/ChIP, SP1 knockdown/overexpression, ANO1 promoter luciferase assay Biochemical and biophysical research communications Medium 30871776
2023 TRPV3 functionally interacts with ANO1 in skin keratinocytes: TRPV3 activation evokes ANO1-mediated Cl- currents; TRPV3 blocker, ANO1 blocker, or low-Cl- medium inhibit keratinocyte migration and proliferation through p38 phosphorylation and cell cycle arrest, implicating chloride influx via ANO1 in wound healing. Patch clamp in NHEKs and mouse keratinocytes, TRPV3 and ANO1 pharmacological blockers, in vitro wound-healing assay, p38 phosphorylation Western blot Communications biology Medium 36690845
2021 TMEM16A is functionally expressed in type I taste bud cells (but not type II or III); ATP (released by type II cells) activates Ca2+-activated Cl- currents through TMEM16A in type I cells via P2Y purinergic receptors; these currents are blocked by the selective inhibitor Ani-9. Immunohistochemistry, whole-cell patch clamp in isolated taste cells, ion substitution experiments, selective TMEM16A blocker Ani-9, ATP stimulation The Journal of physiology Medium 34089532

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature 1106 18724360
2004 The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. The American journal of pathology 477 15215166
2009 Studies on expression and function of the TMEM16A calcium-activated chloride channel. Proceedings of the National Academy of Sciences of the United States of America 263 19965375
2012 TMEM16A induces MAPK and contributes directly to tumorigenesis and cancer progression. Cancer research 259 22564524
2012 DOG1: a novel marker of salivary acinar and intercalated duct differentiation. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 172 22460810
2018 Control of seed dormancy and germination by DOG1-AHG1 PP2C phosphatase complex via binding to heme. Nature communications 151 29875377
2003 FLJ10261 gene, located within the CCND1-EMS1 locus on human chromosome 11q13, encodes the eight-transmembrane protein homologous to C12orf3, C11orf25 and FLJ34272 gene products. International journal of oncology 146 12739008
2012 Dynamic modulation of ANO1/TMEM16A HCO3(-) permeability by Ca2+/calmodulin. Proceedings of the National Academy of Sciences of the United States of America 139 23248295
2010 DOG1 and CD117 are the antibodies of choice in the diagnosis of gastrointestinal stromal tumours. Histopathology 135 20716168
2017 Cell-specific mechanisms of TMEM16A Ca2+-activated chloride channel in cancer. Molecular cancer 125 28893247
2012 TMEM16A/ANO1 channels contribute to the myogenic response in cerebral arteries. Circulation research 120 22872152
2022 The Ca2+-gated channel TMEM16A amplifies capillary pericyte contraction and reduces cerebral blood flow after ischemia. The Journal of clinical investigation 112 35316222
2017 Epithelial Chloride Transport by CFTR Requires TMEM16A. Scientific reports 106 28963502
2014 Inhibition of TMEM16A expression suppresses growth and invasion in human colorectal cancer cells. PloS one 105 25541940
2019 The multifaceted role of TMEM16A in cancer. Cell calcium 103 31279157
2018 Recent advances in TMEM16A: Structure, function, and disease. Journal of cellular physiology 103 30515811
2015 Inhibition of Calcium-Activated Chloride Channel ANO1/TMEM16A Suppresses Tumor Growth and Invasion in Human Lung Cancer. PloS one 103 26305547
2015 ANO1/TMEM16A interacts with EGFR and correlates with sensitivity to EGFR-targeting therapy in head and neck cancer. Oncotarget 93 25823819
2014 ANO1 (TMEM16A) in pancreatic ductal adenocarcinoma (PDAC). Pflugers Archiv : European journal of physiology 93 25163766
2015 Overexpression of ANO1/TMEM16A, an arterial Ca2+-activated Cl- channel, contributes to spontaneous hypertension. Journal of molecular and cellular cardiology 92 25739000
2014 To "grow" or "go": TMEM16A expression as a switch between tumor growth and metastasis in SCCHN. Clinical cancer research : an official journal of the American Association for Cancer Research 88 24919570
2018 TMEM16A is indispensable for basal mucus secretion in airways and intestine. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 87 30586313
2019 Targeting TMEM16A to reverse vasoconstriction and remodelling in idiopathic pulmonary arterial hypertension. The European respiratory journal 78 31023847
2011 Ano1 as a regulator of proliferation. American journal of physiology. Gastrointestinal and liver physiology 78 21940901
2020 Delay of Germination-1 (DOG1): A Key to Understanding Seed Dormancy. Plants (Basel, Switzerland) 73 32283717
2020 The Ca2+-activated chloride channel ANO1/TMEM16A: An emerging therapeutic target for epithelium-originated diseases? Acta pharmaceutica Sinica. B 73 34221860
2014 The Ca(2+) -activated Cl(-) channel, ANO1 (TMEM16A), is a double-edged sword in cell proliferation and tumorigenesis. Cancer medicine 71 24639373
2019 TMEM16A in Cystic Fibrosis: Activating or Inhibiting? Frontiers in pharmacology 70 30761000
2013 DOG1 regulates growth and IGFBP5 in gastrointestinal stromal tumors. Cancer research 69 23576565
2015 Inhibition of ANO1/TMEM16A Chloride Channel by Idebenone and Its Cytotoxicity to Cancer Cell Lines. PloS one 68 26196390
2018 Inhibition of ANO1/TMEM16A induces apoptosis in human prostate carcinoma cells by activating TNF-α signaling. Cell death & disease 66 29899325
2017 Regulation of TMEM16A/ANO1 and TMEM16F/ANO6 ion currents and phospholipid scrambling by Ca2+ and plasma membrane lipid. The Journal of physiology 63 29134661
2022 Hepatocyte-specific TMEM16A deficiency alleviates hepatic ischemia/reperfusion injury via suppressing GPX4-mediated ferroptosis. Cell death & disease 62 36572666
2017 Phosphatidylinositol 4,5-bisphosphate, cholesterol, and fatty acids modulate the calcium-activated chloride channel TMEM16A (ANO1). Biochimica et biophysica acta. Molecular and cell biology of lipids 61 29277655
2014 Activation of Ca(2+) -activated Cl(-) channel ANO1 by localized Ca(2+) signals. The Journal of physiology 58 25398532
2014 The TMEM16A chloride channel as an alternative therapeutic target in cystic fibrosis. The international journal of biochemistry & cell biology 56 24704530
2013 The role of TMEM16A (ANO1) and TMEM16F (ANO6) in cell migration. Pflugers Archiv : European journal of physiology 55 23832500
2020 Arctigenin, a novel TMEM16A inhibitor for lung adenocarcinoma therapy. Pharmacological research 54 32097750
2023 ANO1-Mediated Inhibition of Cancer Ferroptosis Confers Immunotherapeutic Resistance through Recruiting Cancer-Associated Fibroblasts. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 52 37341301
2014 Pharmacological characterization of TMEM16A currents. Channels (Austin, Tex.) 51 24642630
2017 TMEM16A/ANO1 Inhibits Apoptosis Via Downregulation of Bim Expression. Clinical cancer research : an official journal of the American Association for Cancer Research 49 28899969
2016 Knockdown of TMEM16A suppressed MAPK and inhibited cell proliferation and migration in hepatocellular carcinoma. OncoTargets and therapy 49 26834491
2018 Compartmentalized crosstalk of CFTR and TMEM16A (ANO1) through EPAC1 and ADCY1. Cellular signalling 48 29331508
2019 TMEM16A is implicated in the regulation of coronary flow and is altered in hypertension. British journal of pharmacology 45 30710335
2019 Emerging Perspectives on Pain Management by Modulation of TRP Channels and ANO1. International journal of molecular sciences 45 31336748
2018 TRPV4 heats up ANO1-dependent exocrine gland fluid secretion. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 43 29187363
2015 TMEM16A/ANO1 is differentially expressed in HPV-negative versus HPV-positive head and neck squamous cell carcinoma through promoter methylation. Scientific reports 42 26563938
2011 DOG1 and PKC-θ are useful in the diagnosis of KIT-negative gastrointestinal stromal tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 42 21358619
2014 The Ca2+-activated Cl- channel ANO1/TMEM16A regulates primary ciliogenesis. Molecular biology of the cell 40 24694595
2021 Molecular mechanisms of activation and regulation of ANO1-Encoded Ca2+-Activated Cl- channels. Channels (Austin, Tex.) 39 34488544
2017 TMEM16A/ANO1 suppression improves response to antibody-mediated targeted therapy of EGFR and HER2/ERBB2. Genes, chromosomes & cancer 39 28177558
2009 Pancreatic expression of DOG1: a novel gastrointestinal stromal tumor (GIST) biomarker. Applied immunohistochemistry & molecular morphology : AIMM 39 19417627
2020 Hepatocyte TMEM16A Deletion Retards NAFLD Progression by Ameliorating Hepatic Glucose Metabolic Disorder. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 38 32440483
2019 TMEM16A expression in cholinergic neurons of the medial habenula mediates anxiety-related behaviors. EMBO reports 37 31782602
2013 Control of TMEM16A by INO-4995 and other inositolphosphates. British journal of pharmacology 37 22946960
2022 TMEM16A as a potential treatment target for head and neck cancer. Journal of experimental & clinical cancer research : CR 35 35668455
2021 Activation of TMEM16A Ca2+-activated Cl- channels by ROCK1/moesin promotes breast cancer metastasis. Journal of advanced research 35 34603794
2020 Calcium-Activated Chloride Channel ANO1/TMEM16A: Regulation of Expression and Signaling. Frontiers in physiology 35 33250781
2021 TMEM16A Mediates Mucus Production in Human Airway Epithelial Cells. American journal of respiratory cell and molecular biology 34 33026825
2021 The diverse roles of TMEM16A Ca2+-activated Cl- channels in inflammation. Journal of advanced research 32 34603778
2021 TMEM16A, a Homoharringtonine Receptor, as a Potential Endogenic Target for Lung Cancer Treatment. International journal of molecular sciences 32 34681590
2010 Specificity of DOG1 (K9 clone) and protein kinase C theta (clone 27) as immunohistochemical markers of gastrointestinal stromal tumour. Histopathology 32 20716167
2017 The Mechanistic Role of the Calcium-Activated Chloride Channel ANO1 in Tumor Growth and Signaling. Advances in experimental medicine and biology 30 28293832
2023 ANO1 Reprograms Cholesterol Metabolism and the Tumor Microenvironment to Promote Cancer Metastasis. Cancer research 29 36912612
2022 Lysosomal inhibition sensitizes TMEM16A-expressing cancer cells to chemotherapy. Proceedings of the National Academy of Sciences of the United States of America 29 35286200
2019 TMEM16A chloride channel does not drive mucus production. Life science alliance 29 31732694
2016 Relationship between TMEM16A/anoctamin 1 and LRRC8A. Pflugers Archiv : European journal of physiology 29 27514381
2012 Potassium and ANO1/ TMEM16A chloride channel profiles distinguish atypical and typical smooth muscle cells from interstitial cells in the mouse renal pelvis. British journal of pharmacology 29 22014103
2020 ANO1 regulates cardiac fibrosis via ATI-mediated MAPK pathway. Cell calcium 28 33075549
2017 Cell-specific regulation of proliferation by Ano1/TMEM16A in breast cancer with different ER, PR, and HER2 status. Oncotarget 28 29156699
2015 PKCα regulates TMEM16A-mediated Cl⁻ secretion in human biliary cells. American journal of physiology. Gastrointestinal and liver physiology 27 26542395
2015 Is DOG1 Immunoreactivity Specific to Gastrointestinal Stromal Tumor? Cancer control : journal of the Moffitt Cancer Center 27 26678977
2017 Expression of ANO1/DOG1 is associated with shorter survival and progression of breast carcinomas. Oncotarget 26 29416639
2016 HCO3- Transport through Anoctamin/Transmembrane Protein ANO1/TMEM16A in Pancreatic Acinar Cells Regulates Luminal pH. The Journal of biological chemistry 26 27510033
2014 The bestrophin- and TMEM16A-associated Ca(2+)- activated Cl(–) channels in vascular smooth muscles. Channels (Austin, Tex.) 26 25478625
2019 Transcriptional activation of ANO1 promotes gastric cancer progression. Biochemical and biophysical research communications 24 30871776
2019 ANO1/TMEM16A regulates process maturation in radial glial cells in the developing brain. Proceedings of the National Academy of Sciences of the United States of America 24 31147466
2016 Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutations. BMC cancer 24 26867653
2008 Mutation assay of the novel gene DOG1 in gastrointestinal stromal tumors (GISTs). Journal of gastroenterology 24 18648740
2023 Promoter-pervasive transcription causes RNA polymerase II pausing to boost DOG1 expression in response to salt. The EMBO journal 23 36705062
2023 Rare variants in ANO1, encoding a calcium-activated chloride channel, predispose to moyamoya disease. Brain : a journal of neurology 23 37253099
2022 ANO1: More Than Just Calcium-Activated Chloride Channel in Cancer. Frontiers in oncology 23 35734591
2019 Molecular mechanism of TMEM16A regulation: role of CaMKII and PP1/PP2A. American journal of physiology. Cell physiology 23 31461344
2017 The association between the expression of PAR2 and TMEM16A and neuropathic pain. Molecular medicine reports 23 29257338
2016 New Insights on the Regulation of Ca2+ -Activated Chloride Channel TMEM16A. Journal of cellular physiology 23 27682822
2023 Inhibition of TMEM16A improves cisplatin-induced acute kidney injury via preventing DRP1-mediated mitochondrial fission. Acta pharmacologica Sinica 22 37402998
2023 TRPV3-ANO1 interaction positively regulates wound healing in keratinocytes. Communications biology 21 36690845
2023 TMEM16A ion channel: A novel target for cancer treatment. Life sciences 21 37611692
2023 ANO1, CaV1.2, and IP3R form a localized unit of EC-coupling in mouse pulmonary arterial smooth muscle. The Journal of general physiology 21 37702787
2019 Wasted TMEM16A channels are rescued by phosphatidylinositol 4,5-bisphosphate. Cell calcium 21 31683182
2017 Sox10 and DOG1 Expression in Primary Adnexal Tumors of the Skin. The American Journal of dermatopathology 21 28394798
2015 Diagnostic role of DOG1 and p63 immunohistochemistry in salivary gland carcinomas. International journal of clinical and experimental pathology 21 26464669
2017 DNA methylation regulates TMEM16A/ANO1 expression through multiple CpG islands in head and neck squamous cell carcinoma. Scientific reports 20 29123240
2015 CLCA1 and TMEM16A: the link towards a potential cure for airway diseases. Expert review of respiratory medicine 20 26296094
2015 Calmodulin regulation of TMEM16A and 16B Ca(2+)-activated chloride channels. Channels (Austin, Tex.) 18 26083059
2024 The TMEM16A channel as a potential therapeutic target in vascular disease. Current opinion in nephrology and hypertension 17 38193301
2022 Involvement of TMEM16A/ANO1 upregulation in the oncogenesis of colorectal cancer. Biochimica et biophysica acta. Molecular basis of disease 17 35231545
2021 Functional expression of TMEM16A in taste bud cells. The Journal of physiology 17 34089532
2019 Biochemical Inhibition of DOG1/TMEM16A Achieves Antitumoral Effects in Human Gastrointestinal Stromal Tumor Cells In Vitro. Anticancer research 17 31262867
2011 Expression of DOG1, PDGFRA, and p16 in Gastrointestinal Stromal Tumors. Gut and liver 17 21814597

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