Affinage

TM4SF1

Transmembrane 4 L6 family member 1 · UniProt P30408

Length
202 aa
Mass
21.6 kDa
Annotated
2026-06-10
60 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TM4SF1 is a tetraspanin-like plasma membrane glycoprotein that organizes specialized signaling microdomains on endothelial and tumor cells to control cell motility, proliferation, and pathological angiogenesis (PMID:19351819, PMID:38946725). In endothelial cells it is required for filopodia formation, cytokinesis, and the assembly of unusually long, F-actin-poor projections termed 'nanopodia', where it adopts a banded distribution and associates with myosin-10 and β-actin (PMID:19351819, PMID:21626280). TM4SF1 nucleates TM4SF1-enriched microdomains (TMEDs) that recruit signaling molecules including PLCγ and HDAC6; loss of TM4SF1 leaves microtubules hyperacetylated and blocks proliferation, and Tm4sf1-heterozygous mice show impaired tumor growth and wound healing (PMID:38946725). A defining property is its intracellular trafficking: TM4SF1 internalizes from the surface via dynamin-dependent, clathrin-independent vesicles, moves along microtubules, and translocates through nuclear pores into the nucleus, consistent with a cargo-transport role for activated signaling proteins (PMID:26241677, PMID:38946725). Surface TM4SF1 partners with integrins—constitutively with α5/β1 and, after VEGF-A or thrombin stimulation, with αV/β3/β5—and with integrin-α6 to drive a laminin-dependent FAK migration axis (PMID:19351819, PMID:35835740). Across cancers, TM4SF1 acts as a node coupling membrane receptors to oncogenic signaling: it binds DDR1 to promote invadopodia and MMP2/9 activity (PMID:28368050), DVL2 to potentiate Wnt/β-catenin signaling (PMID:31876386), c-Src to activate PI3K/AKT in hepatic stellate cells and drive fibrosis (PMID:40550268), and bridges AKT1–PDPK1 to enhance AKT phosphorylation, thereby suppressing p16/p21-mediated senescence and promoting immune evasion via PD-L1 upregulation and MHC class I loss (PMID:39736265). Its expression is induced by androgen receptor, which binds an androgen response element in the TM4SF1 promoter (PMID:21656834), and by YBX1-mediated m5C stabilization of TM4SF1 mRNA (PMID:41029024). Antibody and antibody-drug-conjugate targeting of TM4SF1's extracellular EL2 loop selectively disrupts newly formed tumor vasculature, establishing it as a vascular therapeutic target (PMID:24986520, PMID:42196417).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2009 High

    Established that TM4SF1 is functionally required for endothelial motility and angiogenesis and physically partners with integrins in a stimulus-dependent manner, defining its role at the cell surface.

    Evidence siRNA knockdown with multiple phenotypic readouts, reciprocal Co-IP for integrin interactions, and an in vivo VEGF-A angiogenesis model in endothelial cells

    PMID:19351819

    Open questions at the time
    • Did not resolve how integrin recruitment is coupled to downstream signaling output
    • Mechanism linking TM4SF1 to cytokinesis and senescence undefined
  2. 2011 High

    Defined a structural/cell-biological role for TM4SF1 in forming nanopodia and identified cytoskeletal binding partners, showing that expression level tunes motility versus projection formation.

    Evidence Live-cell imaging, electron microscopy, adenoviral gain-of-function across cell types, and mass spectrometry pulldown identifying myosin-10 and β-actin

    PMID:21626280

    Open questions at the time
    • Direct versus indirect nature of myosin-10/β-actin association not dissected
    • How TM4SF1 banding pattern is established is unknown
  3. 2011 High

    Identified an upstream transcriptional driver by showing TM4SF1 is a direct androgen receptor target, linking hormone signaling to TM4SF1-dependent cancer cell motility.

    Evidence ChIP demonstrating AR binding to a promoter androgen response element, transcriptomics, siRNA knockdown and wound-healing assays in prostate cancer cells

    PMID:21656834

    Open questions at the time
    • Did not link cytoplasmic relocalization in cancer to a defined trafficking mechanism
    • Downstream effectors of motility not identified here
  4. 2014 Medium

    Validated TM4SF1's extracellular EL2 loop as an actionable surface epitope, providing proof-of-concept for vascular targeting.

    Evidence Monoclonal antibody against EL2 in a humanized Matrigel vessel model in nude mice

    PMID:24986520

    Open questions at the time
    • No direct mechanistic assay of how EL2 engagement disrupts vessels
    • Single antibody reagent, single lab
  5. 2015 High

    Resolved the trafficking itinerary of TM4SF1, demonstrating dynamin-dependent, clathrin-independent internalization and microtubule-mediated nuclear translocation, the basis for its proposed cargo-transporter function.

    Evidence Immuno-nanogold transmission electron microscopy, immunofluorescence, and dynamin inhibition in endothelial cells

    PMID:26241677

    Open questions at the time
    • Cargo carried into the nucleus not identified at this stage
    • Nuclear import machinery (e.g., importin dependence) not defined
  6. 2015 Medium

    Connected TM4SF1 to chemoresistance phenotypes, showing it upregulates multidrug-resistance transporters and modulates PI3K/AKT/mTOR signaling.

    Evidence siRNA/shRNA knockdown with qRT-PCR of ABCB1/ABCC1, Western blots of AKT/mTOR pathway, and orthotopic tumor models in pancreatic and breast cancer cells

    PMID:26464650 PMID:26709920

    Open questions at the time
    • No direct interaction shown linking TM4SF1 to AKT/mTOR components
    • Mechanism of MDR gene induction unresolved
  7. 2017 High

    Placed TM4SF1 upstream of DDR1 in an invadopodia/MMP pathway via a physical interaction and epistatic rescue, mechanistically explaining its pro-invasive activity.

    Evidence Co-IP, double immunofluorescence, siRNA knockdown with DDR1 rescue, invadopodia assays and zymography in pancreatic cancer cells

    PMID:27459514 PMID:28368050

    Open questions at the time
    • Whether TM4SF1-DDR1 binding is direct or microdomain-mediated unresolved
    • Generalizability of DDR1 axis to other tumor types not established here
  8. 2019 Medium

    Extended TM4SF1's signaling reach to Wnt/β-catenin by showing it binds DVL2 and strengthens DVL2-Axin interaction, and linked TM4SF1 induction to oncogenic Kras.

    Evidence Co-IP of TM4SF1-DVL2 and DVL2-Axin, ubiquitination and target-gene readouts in hepatocellular carcinoma

    PMID:31876386

    Open questions at the time
    • Structural basis of DVL2 binding undefined
    • How a membrane protein accesses cytoplasmic DVL2/Axin not addressed
  9. 2019 Low

    Broadened the downstream signaling repertoire by implicating TM4SF1 in ERK1/2 and DDR1-Akt/ERK/mTOR cascades governing proliferation and chemoresistance.

    Evidence Overexpression/knockdown with pharmacological pathway inhibition and Western blots in prostate and lung cancer cells

    PMID:31142317 PMID:31983129

    Open questions at the time
    • Pharmacological epistasis without direct interaction proof
    • Single pathway readout per study, no rescue of DDR1 axis
  10. 2020 Medium

    Linked TM4SF1 to stemness and transcriptional programs through Wnt/β-catenin-c-Myc-SOX2 and YAP-TEAD axes.

    Evidence ChIP of c-Myc at the SOX2 promoter and Co-IP of YAP-TEAD with knockdown/inhibitor rescue in colorectal and lung cancer models

    PMID:32141552 PMID:33153498

    Open questions at the time
    • Direct molecular connection between TM4SF1 and these transcription complexes not defined
    • Whether effects require TMED organization unknown
  11. 2021 Medium

    Positioned TM4SF1 within a senescence-control circuit downstream of AKT and B7-H3 and upstream of SIRT1.

    Evidence RNA-seq, pathway blockade epistasis, and in vivo models in colorectal cancer

    PMID:29175458 PMID:33958586

    Open questions at the time
    • Molecular mechanism by which TM4SF1 modulates SIRT1/PPARγ not established
    • Direct partners in this circuit unidentified
  12. 2022 High

    Defined a laminin-dependent TM4SF1/integrin-α6/FAK migration axis through direct interaction, and identified a lncRNA-transcription-factor route (BCYRN1-BATF) controlling TM4SF1 expression.

    Evidence Co-IP and FAK-inhibitor epistasis with in vivo metastasis (ESCC), plus RIP and ChIP for BCYRN1-BATF promoter regulation (HCC)

    PMID:35730016 PMID:35835740

    Open questions at the time
    • How integrin-α6 engagement activates FAK at TMEDs not detailed
    • Interplay between distinct integrin partners unresolved
  13. 2023 Medium

    Identified MYH9-NOTCH as a downstream effector arm supporting stemness and targeted-therapy resistance.

    Evidence Protein mass spectrometry of downstream targets with in vitro/in vivo validation in lenvatinib-resistant HCC

    PMID:37069693

    Open questions at the time
    • Whether MYH9 regulation is direct unknown
    • Link between MYH9 and NOTCH activation mechanistically incomplete
  14. 2024 High

    Consolidated the unifying model: TM4SF1 builds TMEDs that recruit signaling proteins (PLCγ, HDAC6) and traffic them via microtubules into the nucleus, with HDAC6 sequestration controlling microtubule acetylation and proliferation.

    Evidence Co-recruitment assays for 18 proteins, microtubule acetylation Western blots, and Tm4sf1-heterozygous mouse tumor/wound models

    PMID:38946725

    Open questions at the time
    • Stoichiometry and selectivity of TMED recruitment not fully defined
    • How nuclear-delivered cargo exerts proliferative effect unresolved
  15. 2024 High

    Established a direct scaffolding mechanism whereby TM4SF1 bridges AKT1 and PDPK1 to drive AKT phosphorylation, coupling senescence suppression to immune evasion, and identified PLAU and TSPAN1 as physical partners plus YBX1/m5C as an mRNA-stabilizing regulator.

    Evidence IP-MS, Co-IP, BiFC and flow cytometry (AKT1-PDPK1; PD-L1/MHC-I), Co-IP for PLAU and TSPAN1, and m5C-RIP with mRNA stability assays (YBX1)

    PMID:38229120 PMID:39060768 PMID:39736265 PMID:41029024

    Open questions at the time
    • Whether AKT1/PDPK1 bridging occurs at the membrane or after internalization unknown
    • Relative contribution of PLAU and TSPAN1 to AKT activation not compared
  16. 2025 High

    Demonstrated a non-cancer disease role through a direct TM4SF1-c-Src interaction driving hepatic stellate cell activation and fibrosis, and confirmed selective TM4SF1 expression/internalization on neovasculature for ADC targeting.

    Evidence Co-IP, HSC-specific knockout mice and saracatinib rescue (fibrosis); in vivo TM4SF1-directed ADC homing to VEGF-A164-induced vessels

    PMID:40550268 PMID:42196417

    Open questions at the time
    • Whether c-Src binding uses the same interface as other kinase partners unknown
    • Determinants of TM4SF1 selectivity for nascent versus mature vessels undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved which activated cargo proteins TM4SF1 physically delivers to the nucleus and how this nuclear function mechanistically drives proliferation, distinct from its membrane scaffolding roles.
  • No defined nuclear substrate-to-phenotype mechanism
  • Importin/nuclear-pore dependence of cargo not biochemically dissected
  • Structural basis distinguishing constitutive versus stimulus-induced partner binding unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3 GO:0140104 molecular carrier activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005634 nucleus 2 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1474244 Extracellular matrix organization 2
Partners
DDR1DVL2ITGA5ITGA6ITGB1PDPK1SRCTSPAN1
Complex memberships
TM4SF1-enriched microdomains (TMEDs)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 TM4SF1 knockdown in endothelial cells prevented filopodia formation, inhibited cell mobility, blocked cytokinesis, and rendered cells senescent. Integrin-α5 and integrin-β1 subunits interacted constitutively with TM4SF1, whereas integrin subunits αV, β3, β5 interacted with TM4SF1 only after VEGF-A or thrombin stimulation. TM4SF1 knockdown substantially inhibited maturation of VEGF-A164-induced angiogenesis in vivo. siRNA knockdown, Co-immunoprecipitation, in vivo tumor angiogenesis model Cancer research High 19351819
2011 TM4SF1 is necessary for formation of unusually long, thin (~100–300 nm wide), F-actin-poor endothelial cell projections called 'nanopodia'. TM4SF1 localizes in a regularly spaced banded pattern within nanopodia. Live cell imaging showed nanopodia are projected during migration and intercellular interactions. Mass spectrometry demonstrated TM4SF1 interacted with myosin-10 and β-actin. When TM4SF1 was overexpressed (~400 copies/cell vs normal ~90), cells formed more/longer nanopodia but could not polarize or migrate. When expressed at EC-like levels in fibroblasts (~5 normally), cells formed TM4SF1-banded nanopodia and EC-like lamellipodia. Live cell imaging (GFP-transduced HUVEC), adenoviral overexpression, immunostaining (light and electron microscopy), mass spectrometry pulldown Angiogenesis High 21626280
2011 TM4SF1 is a direct transcriptional target of the androgen receptor (AR); a functional androgen response element was identified in the TM4SF1 promoter by chromatin immunoprecipitation. TM4SF1 mediates prostate cancer cell motility; siRNA knockdown inhibited cell migration. In normal prostate epithelium TM4SF1 localizes apically, whereas in prostate cancer cells it localizes predominantly in the cytoplasm. Chromatin immunoprecipitation (ChIP), transcriptomic analysis, siRNA knockdown, wound healing assay, immunohistochemistry The Prostate High 21656834
2014 Monoclonal antibodies against TM4SF1's extracellular loop-2 (EL2) domain disrupted human tumor vasculature in a humanized Matrigel plug model and eliminated incorporated PC3 prostate cancer cells, validating TM4SF1 as a therapeutic vascular target. Monoclonal antibody generation and in vivo humanized vessel model (ECFC/MSC Matrigel implants in nude mice) Angiogenesis Medium 24986520
2015 TM4SF1 is internalized from the plasma membrane of endothelial cells via uncoated cytoplasmic vesicles in a dynamin-dependent, clathrin-independent manner, then transported along microtubules through the cytoplasm and through nuclear pores into the nucleus, as demonstrated by immuno-nanogold transmission electron microscopy. Immuno-nanogold transmission electron microscopy, immunofluorescence microscopy, dynamin inhibition Biochemical and biophysical research communications High 26241677
2015 TM4SF1 promotes gemcitabine resistance in pancreatic cancer cells by upregulating multidrug resistance genes ABCB1 and ABCC1; silencing TM4SF1 increased gemcitabine sensitivity both in vitro and in vivo in orthotopic tumor models. siRNA knockdown, shRNA lentiviral knockdown, qRT-PCR for MDR genes, cell proliferation/apoptosis assays, orthotopic tumor model with bioluminescent imaging PloS one Medium 26709920
2015 TM4SF1 promotes breast cancer cell migration via the PI3K/AKT/mTOR pathway; silencing TM4SF1 decreased phosphorylated AKT, p-mTOR, and p-P70S6K levels, while overexpression increased cell migration and decreased apoptosis. siRNA knockdown, plasmid overexpression, Western blotting of PI3K/AKT/mTOR pathway components, Matrigel migration assay, flow cytometry International journal of clinical and experimental pathology Low 26464650
2016 TM4SF1 knockdown in pancreatic cancer cells reduced migration and invasion and downregulated the expression and enzymatic activity of MMP-2 and MMP-9, as measured by gelatin zymography. siRNA/shRNA knockdown, Transwell migration/invasion assay, gelatin zymography, Western blot, orthotopic tumor model Cellular physiology and biochemistry Medium 27459514
2017 TM4SF1 co-localizes with DDR1 and physically interacts with DDR1 (by co-immunoprecipitation and double immunofluorescence) in pancreatic cancer cells. TM4SF1 silencing reduced DDR1 expression, impaired invadopodia formation and function, and decreased MMP2 and MMP9 expression; restoring DDR1 rescued these effects, placing TM4SF1 upstream of DDR1-MMP2/9 in an invadopodia-promoting pathway. Co-immunoprecipitation, double immunofluorescence co-staining, siRNA knockdown, rescue overexpression of DDR1, invadopodia formation assay, qRT-PCR Scientific reports High 28368050
2017 TM4SF1 regulates apoptosis, cell cycle, and ROS metabolism in bladder cancer cells via the PPARγ-SIRT1 feedback loop; knockdown of TM4SF1 induced cell cycle arrest and apoptosis associated with ROS upregulation, and these effects were reversed by GW9662 (PPARγ antagonist) or resveratrol (SIRT1 activator). siRNA knockdown, flow cytometry (cell cycle/apoptosis), ROS measurement, pharmacological rescue with GW9662 and resveratrol, in vivo xenograft Cancer letters Medium 29175458
2019 TM4SF1 promotes non-small cell lung cancer proliferation, invasion, and chemo-resistance by regulating the expression of DDR1 and its downstream Akt/ERK/mTOR pathway; silencing TM4SF1 reduced DDR1 expression and Akt/ERK/mTOR signaling, enhancing sensitivity to cisplatin and paclitaxel. siRNA knockdown, Western blotting (DDR1, p-AKT, p-ERK, mTOR), MTS/clonogenic assay, Transwell assay, flow cytometry, RT-PCR Respiratory research Medium 31142317
2019 TM4SF1 is an interacting partner of DVL2 in hepatocellular carcinoma; TM4SF1 overexpression strengthened the DVL2-Axin interaction, leading to activation of Wnt/β-catenin signaling (increased Axin2 and cyclin D1 expression and decreased β-catenin ubiquitination). TM4SF1 expression was induced by Kras signaling. Co-immunoprecipitation (TM4SF1-DVL2 and DVL2-Axin interactions), Western blotting, overexpression and knockdown, ubiquitination assay, Kras pathway analysis Journal of cellular and molecular medicine Medium 31876386
2019 TM4SF1 overexpression in prostate cancer cells activated ERK1/2 signaling; suppression of ERK1/2 reversed the pro-migratory, pro-invasive, and pro-proliferative effects of TM4SF1 overexpression, placing TM4SF1 upstream of ERK1/2. Plasmid overexpression, pharmacological ERK1/2 inhibition, Transwell assay, wound-healing assay, colony formation, EdU staining, Western blotting Journal of B.U.ON. Low 31983129
2020 TM4SF1 modulates SOX2 expression in a Wnt/β-catenin activation-dependent manner in colorectal cancer; TM4SF1 knockdown reduced c-Myc expression and c-Myc binding to the SOX2 gene promoter, suppressing EMT (TGF-β1-mediated) and cancer stemness. siRNA knockdown, GSEA pathway analysis, Western blotting, ChIP (c-Myc binding to SOX2 promoter), TGF-β1 stimulation, sphere formation assay, xenograft mouse model Journal of experimental & clinical cancer research Medium 33153498
2020 TM4SF1 regulates YAP-TEAD interaction in non-small cell lung cancer; TM4SF1 modulated the YAP-TEAD protein-protein interaction and downstream target gene levels, as shown by Co-IP; sh-YAP or YAP-TEAD inhibitor (Peptide 17) reversed TM4SF1-mediated oncogenic effects. Co-immunoprecipitation, siRNA/shRNA knockdown, plasmid overexpression, pharmacological inhibition (Peptide 17), Western blotting, xenograft tumor model European review for medical and pharmacological sciences Medium 32141552
2021 B7-H3 prevents cellular senescence in colorectal cancer through the AKT/TM4SF1/SIRT1 pathway; blocking this pathway reversed B7-H3-induced resistance to DOX-induced senescence, placing TM4SF1 downstream of AKT and upstream of SIRT1. RNA-seq, Western blotting, siRNA knockdown/overexpression of B7-H3, pathway blockade experiments, in vivo tumor model Cell death & disease Medium 33958586
2022 TM4SF1 promotes esophageal squamous cell carcinoma cell adhesion, spreading, migration, and invasion in a laminin-dependent manner by physically interacting with integrin α6; the TM4SF1/integrin α6/FAK signaling axis mediates cell migration under laminin-coating conditions, and FAK inhibition or TM4SF1 knockdown attenuated migration and lung metastasis. Co-immunoprecipitation, immunofluorescence co-staining, siRNA knockdown, FAK inhibitor treatment, Transwell migration/invasion assay, in vivo lung metastasis model Cell death & disease High 35835740
2023 TM4SF1 upregulates MYH9 expression, which activates the NOTCH pathway, thereby promoting cancer stemness and lenvatinib resistance in hepatocellular carcinoma; this pathway was identified by protein mass spectrometry and validated by in vitro and in vivo experiments. Protein mass spectrometry (downstream protein identification), bioinformatics, in vitro and in vivo functional assays, Western blotting, lenvatinib-resistant cell line model Biology direct Medium 37069693
2024 TM4SF1 forms 'TM4SF1-enriched microdomains' (TMEDs) on the endothelial cell surface that recruit signaling molecules (12 of 18 examined, notably PLCγ and HDAC6) and internalize along microtubules to intracellular locations including the nucleus. When TM4SF1 is knocked down, microtubules become heavily acetylated (despite normal HDAC6 protein levels) and cells are unable to proliferate. Tumor growth and wound healing are inhibited in Tm4sf1-heterozygous mice. Co-localization immunofluorescence, protein co-recruitment assays to TMEDs, siRNA knockdown, microtubule acetylation Western blot, Tm4sf1-heterozygous mouse in vivo models Journal of cell communication and signaling High 38946725
2024 TM4SF1 enhances the interaction between AKT1 and PDPK1 (as shown by co-immunoprecipitation, bimolecular fluorescence complementation, and immunofluorescence), promoting AKT phosphorylation, which subsequently downregulates p16 and p21, suppressing tumor cell senescence. TM4SF1-mediated AKT phosphorylation also enhances PD-L1 expression and reduces MHC class I levels on tumor cells, impairing CD8+ T cell cytotoxic function. Immunoprecipitation-mass spectrometry, co-immunoprecipitation, bimolecular fluorescence complementation, immunofluorescence, flow cytometry, SA-β-gal activity assay, Western blot, hydrodynamic tail vein injection mouse model Clinical and molecular hepatology High 39736265
2024 PLAU physically interacts with TM4SF1 to promote Akt signaling activation in non-small cell lung cancer; TM4SF1 knockdown or treatment with anti-TM4SF1 neutralizing antibody inhibited PLAU-induced growth, survival, and cisplatin resistance, placing TM4SF1 as a required mediator of PLAU-driven Akt activation. Co-immunoprecipitation (PLAU-TM4SF1 interaction), siRNA knockdown, plasmid overexpression, neutralizing antibody treatment, in vivo xenograft Biology direct Medium 38229120
2025 TM4SF1 in hepatic stellate cells binds to and activates the tyrosine kinase c-Src, promoting HSC activation and hepatic fibrosis via the c-Src/PI3K/AKT pathway; HSC-specific TM4SF1 knockout mice showed reduced HSC activation and attenuated hepatic fibrosis, and the Src family inhibitor saracatinib blocked TM4SF1 overexpression-induced fibrosis. Co-immunoprecipitation (TM4SF1-c-Src interaction), HSC-specific knockout mouse model, pharmacological inhibition (saracatinib), overexpression/knockdown in LX-2 cells, Western blotting, in vivo fibrosis models Cellular and molecular gastroenterology and hepatology High 40550268
2025 TM4SF1-directed ADC (3m2A7A-LP2) specifically homed to and disrupted newly formed VEGF-A164-induced angiogenic blood vessels within 48 hours in a mouse ear model, without affecting normal vessels in the same animal, demonstrating that TM4SF1 is selectively expressed on and internalized by newly forming tumor blood vessels. Adenoviral VEGF-A164 ear model in nude mice, in vivo ADC targeting/homing assay, histological analysis, multi-dose treatment International journal of molecular sciences Medium 42196417
2024 YBX1, an RNA-binding protein, stabilizes TM4SF1 mRNA via m5C (5-methylcytosine) modification, upregulating TM4SF1 expression and subsequently activating β-catenin/c-Myc signaling to drive bladder cancer proliferation and glycolysis; overexpression of β-catenin reversed the inhibitory effects of TM4SF1 silencing. RNA immunoprecipitation (RIP), m5C-RIP, Actinomycin D mRNA stability assay, luciferase reporter assay, siRNA knockdown, overexpression, Western blotting, glycolysis assays Combinatorial chemistry & high throughput screening Medium 41029024
2024 TSPAN1 physically interacts with TM4SF1 in glioblastoma stem cells (confirmed by Co-IP and immunofluorescence); the compound 4,5-dimethoxycanthin-6-one inhibited both TM4SF1 and TSPAN1 expression and disrupted this interaction, suppressing glioblastoma stem cell formation and proliferation; TSPAN1 overexpression partially reversed these effects. Co-immunoprecipitation, immunofluorescence, molecular docking simulation, CCK-8/colony formation, wound healing, Transwell, flow cytometry, xenograft mouse model Neurochemical research Medium 39060768
2022 The lncRNA BCYRN1 recruits the transcription factor BATF to the TM4SF1 promoter, thereby upregulating TM4SF1 expression; ChIP demonstrated BATF binding to the TM4SF1 promoter, and RNA immunoprecipitation confirmed BCYRN1-BATF interaction. Knockdown of BCYRN1 reduced TM4SF1-dependent HCC cell migration, invasion, and xenograft tumor growth. RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), luciferase reporter assay, siRNA knockdown, in vivo xenograft Disease markers Medium 35730016

Source papers

Stage 0 corpus · 60 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 TM4SF1 promotes EMT and cancer stemness via the Wnt/β-catenin/SOX2 pathway in colorectal cancer. Journal of experimental & clinical cancer research : CR 285 33153498
2009 The L6 protein TM4SF1 is critical for endothelial cell function and tumor angiogenesis. Cancer research 84 19351819
2017 TM4SF1 regulates apoptosis, cell cycle and ROS metabolism via the PPARγ-SIRT1 feedback loop in human bladder cancer cells. Cancer letters 70 29175458
2016 MicroRNA-9 suppresses cell migration and invasion through downregulation of TM4SF1 in colorectal cancer. International journal of oncology 66 26983891
2013 hsa-miR-141 downregulates TM4SF1 to inhibit pancreatic cancer cell invasion and migration. International journal of oncology 61 24285464
2016 TM4SF1 Promotes Proliferation, Invasion, and Metastasis in Human Liver Cancer Cells. International journal of molecular sciences 58 27153056
2018 MiRNA-206 suppresses PGE2-induced colorectal cancer cell proliferation, migration, and invasion by targetting TM4SF1. Bioscience reports 54 30135139
2011 TM4SF1: a tetraspanin-like protein necessary for nanopodia formation and endothelial cell migration. Angiogenesis 53 21626280
2017 TM4SF1 Promotes Metastasis of Pancreatic Cancer via Regulating the Expression of DDR1. Scientific reports 47 28368050
2017 MicroRNA-30a-5p (miR-30a) regulates cell motility and EMT by directly targeting oncogenic TM4SF1 in colorectal cancer. Journal of cancer research and clinical oncology 47 28528497
2019 Transmembrane-4 L-six family member-1 (TM4SF1) promotes non-small cell lung cancer proliferation, invasion and chemo-resistance through regulating the DDR1/Akt/ERK-mTOR axis. Respiratory research 44 31142317
2011 TM4SF1, a novel primary androgen receptor target gene over-expressed in human prostate cancer and involved in cell migration. The Prostate 44 21656834
2014 TM4SF1: a new vascular therapeutic target in cancer. Angiogenesis 42 24986520
2015 Novel Anti-TM4SF1 Antibody-Drug Conjugates with Activity against Tumor Cells and Tumor Vasculature. Molecular cancer therapeutics 40 26089370
2015 TM4SF1 Promotes Gemcitabine Resistance of Pancreatic Cancer In Vitro and In Vivo. PloS one 39 26709920
2016 TM4SF1 Regulates Pancreatic Cancer Migration and Invasion In Vitro and In Vivo. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 37 27459514
2015 Role of TM4SF1 in regulating breast cancer cell migration and apoptosis through PI3K/AKT/mTOR pathway. International journal of clinical and experimental pathology 37 26464650
2018 miR-30 Family Reduction Maintains Self-Renewal and Promotes Tumorigenesis in NSCLC-Initiating Cells by Targeting Oncogene TM4SF1. Molecular therapy : the journal of the American Society of Gene Therapy 35 30301667
2021 B7-H3 suppresses doxorubicin-induced senescence-like growth arrest in colorectal cancer through the AKT/TM4SF1/SIRT1 pathway. Cell death & disease 34 33958586
2023 TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC. Biology direct 32 37069693
2020 TM4SF1 involves in miR-1-3p/miR-214-5p-mediated inhibition of the migration and proliferation in keloid by regulating AKT/ERK signaling. Life sciences 25 32376266
2019 TM4SF1 is a potential target for anti-invasion and metastasis in ovarian cancer. BMC cancer 23 30876464
2022 TM4SF1 promotes esophageal squamous cell carcinoma metastasis by interacting with integrin α6. Cell death & disease 22 35835740
2019 TM4SF1, a binding protein of DVL2 in hepatocellular carcinoma, positively regulates beta-catenin/TCF signalling. Journal of cellular and molecular medicine 22 31876386
2023 TM4SF1-AS1 inhibits apoptosis by promoting stress granule formation in cancer cells. Cell death & disease 21 37443145
2018 Clinical significance of TM4SF1 as a tumor suppressor gene in gastric cancer. Cancer medicine 20 29665316
2017 TM4SF1 promotes the self-renewal of esophageal cancer stem-like cells and is regulated by miR-141. Oncotarget 20 27974706
2018 microRNA-520f inhibits hepatocellular carcinoma cell proliferation and invasion by targeting TM4SF1. Gene 19 29505836
2020 lncRNA TM4SF1-AS1 Activates the PI3K/AKT Signaling Pathway and Promotes the Migration and Invasion of Lung Cancer Cells. Cancer management and research 17 32765064
2023 Construction of CAR-T cells targeting TM4SF1 and its anti-tumor capacity in ovarian cancer. Immunology letters 16 36739093
2021 HIF-1α-activated TM4SF1-AS1 promotes the proliferation, migration, and invasion of hepatocellular carcinoma cells by enhancing TM4SF1 expression. Biochemical and biophysical research communications 16 34118595
2015 Intracellular distribution of TM4SF1 and internalization of TM4SF1-antibody complex in vascular endothelial cells. Biochemical and biophysical research communications 15 26241677
2024 PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1. Biology direct 14 38229120
2024 Targeting TM4SF1 promotes tumor senescence enhancing CD8+ T cell cytotoxic function in hepatocellular carcinoma. Clinical and molecular hepatology 13 39736265
2024 NUP43 promotes PD-L1/nPD-L1/PD-L1 feedback loop via TM4SF1/JAK/STAT3 pathway in colorectal cancer progression and metastatsis. Cell death discovery 12 38762481
2023 Tm4sf1-marked Endothelial Subpopulation Is Dysregulated in Pulmonary Arterial Hypertension. American journal of respiratory cell and molecular biology 12 36252184
2018 TM4SF1 inhibits apoptosis and promotes proliferation, migration and invasion in human gastric cancer cells. Oncology letters 12 30344751
2023 Three Members of Transmembrane-4-Superfamily, TM4SF1, TM4SF4, and TM4SF5, as Emerging Anticancer Molecular Targets against Cancer Phenotypes and Chemoresistance. Pharmaceuticals (Basel, Switzerland) 11 36678607
2021 LINC02308 promotes the progression of glioma through activating mTOR/AKT-signaling pathway by targeting miR-30e-3p/TM4SF1 axis. Cell biology and toxicology 11 33945031
2020 TM4SF1 facilitates non-small cell lung cancer progression through regulating YAP-TEAD pathway. European review for medical and pharmacological sciences 11 32141552
2021 Effect and mechanism of downregulating the long-chain noncoding RNA TM4SF1-AS1 on the proliferation, apoptosis and invasion of gastric cancer cells. World journal of surgical oncology 10 34330293
2025 Bladder cancer variants share aggressive features including a CA125+ cell state and targetable TM4SF1 expression. Nature communications 9 40527915
2019 Over-expression of TM4SF1 improves cell metastasis and growth by activating ERK1/2 signaling pathway in human prostate cancer. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 8 31983129
2022 Long Noncoding RNA BCYRN1 Recruits BATF to Promote TM4SF1 Upregulation and Enhance HCC Cell Proliferation and Invasion. Disease markers 6 35730016
2024 Identification and characterization of TM4SF1+ tumor self-seeded cells. Cell reports 4 39003738
2022 Hyper-expression and hypomethylation of TM4SF1 are associated with lymph node metastases in papillary thyroid carcinoma patients. Neoplasma 4 35081723
2022 TM4SF1 promotes glioma malignancy through multiple mechanisms. Neoplasma 4 35532297
2024 TM4SF1 is a molecular facilitator that distributes cargo proteins intracellularly in endothelial cells in support of blood vessel formation. Journal of cell communication and signaling 3 38946725
2022 lncRNA TM4SF1-AS1 predicts dismal outcomes and promotes cholangiocarcinoma progression via modulating miR-744-3p. Clinics and research in hepatology and gastroenterology 3 35346892
2024 Breast cancer malignancy is governed by regulation of the macroH2A2/TM4SF1 axis, the AKT/NF-κB pathway, and elevated MMP13 expression. Molecular carcinogenesis 2 38251858
2025 TM4SF1 overexpression in tumor-associated endothelial cells promotes microvascular invasion in hepatocellular carcinoma. Frontiers in oncology 1 40123905
2025 YBX1 Enhances the Stability of TM4SF1 in an m5C-Dependent Manner to Promote Bladder Cancer Proliferation and Glycolysis. Combinatorial chemistry & high throughput screening 1 41029024
2022 MicroRNA-501-3p targeting TM4SF1 facilitates tumor-related behaviors of gastric cancer cells via EMT signaling pathway. Mutation research 1 36274500
2014 [Construction of a eukaryotic expression vector of TM4SF1 and its effect on migration and invasion of colorectal cancer cells]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 1 24968843
2026 TM4SF1 regulates esophageal squamous cell carcinoma KYSE150 cell phenotypes via miRNA-regulated pathways. Cytotechnology 0 42040328
2026 TM4SF1-Directed Antibody-Drug Conjugates Selectively Destroy Newly Formed Blood Vessels Induced by VEGF-A. International journal of molecular sciences 0 42196417
2025 Hepatic Stellate Cell TM4SF1 Accelerates Hepatic Fibrosis Progression via Interacting With the Tyrosine Kinase c-Src. Cellular and molecular gastroenterology and hepatology 0 40550268
2025 Cable Cars to the Nucleus: TM4SF1-Enriched Microdomains Conduct Signaling in Endothelial Cells for Blood Vessel Formation. International journal of molecular sciences 0 41226530
2024 4,5-Dimethoxycanthin-6-one Inhibits Glioblastoma Stem Cell and Tumor Growth by Inhibiting TSPAN1 Interaction with TM4SF1. Neurochemical research 0 39060768
2020 Erratum: lncRNA TM4SF1-AS1 Activates the PI3K/AKT Signaling Pathway and Promotes the Migration and Invasion of Lung Cancer Cells [Corrigendum]. Cancer management and research 0 32982403

Missed literature

Know a paper Affinage missed for TM4SF1? Flag it for the maintainers and the community.

No submissions yet.