Affinage

TSPAN8

Tetraspanin-8 · UniProt P19075

Length
237 aa
Mass
26.0 kDa
Annotated
2026-04-28
70 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TSPAN8 is a tetraspanin that organizes membrane microdomains to coordinate integrin-mediated adhesion, cell migration, extracellular vesicle biogenesis, and receptor signaling across epithelial, endothelial, and stromal compartments. At the plasma membrane, TSPAN8 forms complexes with integrins (α6β4, α6β1, α3β1), E-cadherin, and p120-catenin to regulate adhesion–motility switching through Src/FAK/Ras activation and MMP-dependent matrix remodeling, and it selectively loads cargo into exosomes that drive VEGF-independent angiogenesis and paracrine Hedgehog pathway activation in recipient cells (PMID:15837731, PMID:20858717, PMID:23683890, PMID:20124479, PMID:31253779). TSPAN8 also undergoes EGFR–AKT-dependent phosphorylation at Ser129, enabling 14-3-3θ/importin-β1-mediated nuclear translocation where it co-activates STAT3 target genes, and in prostate cancer it stabilizes AR/AR-V7 through mutual protection from MDM2-mediated ubiquitination (PMID:35197608, PMID:26649804, PMID:36951301, PMID:38410785). Beyond tumor biology, TSPAN8 directs IFN-γR1 into lipid-raft endocytic routes to restrain STAT1 signaling and maintain intestinal epithelial barrier integrity, interacts with ECE1 to amplify endothelin-1 production, and is required for ventral–dorsal pancreatic bud fusion during Xenopus development (PMID:37204469, PMID:37835445, PMID:19403659).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 Medium

    Establishing TSPAN8 as a metastasis-associated tetraspanin that partners with integrins: transfection of D6.1A into a low-metastasizing line proved that TSPAN8 expression is sufficient to increase metastatic potential and demonstrated the first integrin partner (α6β1).

    Evidence cDNA transfection and Co-IP in rat tumor lines

    PMID:9531564

    Open questions at the time
    • No reciprocal validation of integrin interaction with purified proteins
    • Mechanism linking integrin association to metastasis not defined
  2. 2005 Medium

    Defining how TSPAN8–integrin complexes regulate cell behavior: PKC-induced strengthening of the TSPAN8–α6β4 complex caused integrin internalization, decreased laminin adhesion, and increased migration, linking tetraspanin–integrin dynamics to a motility switch.

    Evidence Co-IP, PKC activation, migration assay in human pancreatic carcinoma cells

    PMID:15837731

    Open questions at the time
    • PKC substrate specificity on TSPAN8 or integrin not identified
    • In vivo relevance not tested
  3. 2006 Medium

    Revealing TSPAN8 as a driver of angiogenesis: tumor-cell and exosome-expressed TSPAN8 induced MMP/uPA secretion and VEGF/VEGFR upregulation, establishing a non-cell-autonomous pro-angiogenic role.

    Evidence In vivo angiogenesis assay with anti-D6.1A antibody blocking

    PMID:16849554

    Open questions at the time
    • Direct molecular mechanism linking TSPAN8 to VEGF induction unclear
    • Exosome-specific versus cell-surface contribution not separated
  4. 2009 Medium

    Demonstrating a developmental role for TSPAN8: morpholino knockdown in Xenopus showed TSPAN8 is required for dorsal–ventral pancreatic bud fusion and acinar differentiation, broadening its biology beyond cancer.

    Evidence Morpholino knockdown and mRNA overexpression in Xenopus embryos

    PMID:19403659

    Open questions at the time
    • Mammalian pancreatic development role not confirmed
    • Downstream signaling pathway mediating bud fusion unknown
  5. 2010 High

    Elucidating TSPAN8's role in exosome cargo selection and VEGF-independent angiogenesis: Tspan8–CD49d complexes selectively recruited proteins and mRNA into exosomes that were preferentially taken up by endothelial cells, activating angiogenic gene programs independently of VEGF.

    Evidence Exosome isolation, Co-IP, gene expression profiling, EC functional assays

    PMID:20124479

    Open questions at the time
    • Sorting signal within TSPAN8 for exosome loading not mapped
    • Whether TSPAN8 functions as cargo receptor or scaffold not resolved
  6. 2010 High

    Dissecting TSPAN8 internalization and adhesion-complex remodeling: TSPAN8's N-terminal region recruits intersectin-2 into clathrin-dependent complexes with CD49d, explaining how activation-induced TSPAN8 endocytosis couples to reduced adhesion and enhanced migration, and how TSPAN8 interacts with E-cadherin and p120-catenin to switch between collagen-binding integrins α1β1 and α2β1.

    Evidence Chimera internalization assays, chemical cross-linking, Co-IP, siRNA knockdown, migration assays

    PMID:20858717 PMID:20937409

    Open questions at the time
    • Structural basis of TSPAN8–E-cadherin interaction not resolved
    • Whether intersectin-2 route and E-cadherin complex operate in the same cell context unclear
  7. 2013 Medium

    Mapping TSPAN8 signaling downstream of integrin β4: TSPAN8 recruits β4 integrin, promotes its phosphorylation and Src/FAK/Ras activation, shifting cells from adhesion to motility, while CD151 preferentially associates with MMPs—establishing non-redundant tetraspanin functions.

    Evidence Stable knockdown, Co-IP, phosphorylation and signaling assays in rat pancreatic adenocarcinoma

    PMID:23683890

    Open questions at the time
    • Kinase responsible for β4 phosphorylation not identified
    • Whether TSPAN8 and CD151 compete for the same integrin pools unclear
  8. 2015 High

    Discovering TSPAN8 nuclear localization and AR stabilization: TSPAN8 was found in the nucleus of prostate cancer cells in an AR-dependent manner, directly interacting with AR and reducing its ubiquitin-proteasomal degradation, establishing TSPAN8 as a transcriptional co-regulator.

    Evidence Co-IP, nuclear fractionation, in vitro interaction assay, siRNA knockdown

    PMID:26649804

    Open questions at the time
    • Deubiquitinase mediating AR stabilization by TSPAN8 not identified at this point
    • Mechanism of TSPAN8 nuclear import not defined
  9. 2018 High

    In vivo genetic validation: Tspan8/CD151 knockout mice showed impaired tumor dissemination with distorted tetraspanin–integrin–protease networks, and host-derived Tspan8-containing exosomes promoted angiogenesis through GPCR/RTK associations in endothelial cells.

    Evidence Knockout mice, tumor implantation, exosome coculture, Co-IP, rescue experiments

    PMID:30541597

    Open questions at the time
    • Single vs. double KO contributions not fully deconvoluted
    • Identity of specific GPCR/RTK partners on endothelial cells not determined
  10. 2019 High

    Linking TSPAN8 to Hedgehog pathway and cancer stemness: TSPAN8 recruited deubiquitinase ATXN3 to stabilize the SHH/PTCH1 complex, enabling SMO ciliary translocation and downstream Hh signaling that drove NANOG/OCT4 expression and chemoresistance; a β-catenin–TSPAN8 positive feedback loop was simultaneously identified in melanoma and colorectal cancer.

    Evidence Co-IP, ubiquitination assay, confocal cilia imaging, ChIP for β-catenin on TSPAN8 promoter, in vivo tumor formation

    PMID:30679790 PMID:31253779 PMID:31838484

    Open questions at the time
    • Whether ATXN3 recruitment is direct or scaffold-mediated not resolved
    • Intersection between Hh and β-catenin feedback loops not explored
  11. 2022 High

    Defining the nuclear import mechanism: EGFR–AKT phosphorylates TSPAN8 at Ser129, creating a 14-3-3θ binding site that enables importin-β1-mediated nuclear translocation; nuclear phospho-TSPAN8 enhances STAT3 chromatin occupancy at MYC, BCL2, and MMP9 promoters.

    Evidence In vitro kinase assay, phospho-site mutagenesis, ChIP, nuclear fractionation, anti-TSPAN8 antibody in vivo

    PMID:35197608

    Open questions at the time
    • Whether nuclear TSPAN8–STAT3 complex requires additional co-factors unknown
    • Relationship between AR-dependent and EGFR-dependent nuclear import not clarified
  12. 2023 High

    Extending the AR co-regulator role: TSPAN8 was shown to interact with AR-V7 in addition to full-length AR, with mutual deubiquitination enabling both proteins' stabilization and co-recruitment to AR/AR-V7-regulated gene promoters; separately, TSPAN8 was found to direct IFN-γR1 into lipid-raft endocytosis to restrain STAT1 signaling and maintain intestinal barrier integrity, and to complex with ECE1 to amplify endothelin-1 production.

    Evidence Co-IP, ubiquitination assay, ChIP, lipid raft fractionation, ECE1 activity assay in Tspan8 KO mouse tissue

    PMID:36951301 PMID:37204469 PMID:37835445

    Open questions at the time
    • Deubiquitinase responsible for AR/TSPAN8 mutual stabilization still unidentified
    • Whether ECE1 activation is direct or via membrane microdomain organization not established
  13. 2024 High

    Revealing a stromal metabolic reprogramming function: in myofibroblastic cancer-associated fibroblasts, TSPAN8 recruits MAPK11 to phosphorylate E3 ligase RBBP6 at Ser772, triggering SIRT6 degradation and upregulating GLS1/PYCR1-dependent aspartate and proline secretion that feeds tumor cell outgrowth; MDM2 was identified as the E3 ligase mediating ubiquitination of TSPAN8, AR, and AR-V7.

    Evidence Co-IP, phosphorylation assay, metabolite measurement, in vivo xenograft; systematic E3 ligase siRNA screen with MDM2 inhibitor

    PMID:38410785 PMID:38569015

    Open questions at the time
    • Whether MAPK11 recruitment is a general TSPAN8 function or CAF-specific unknown
    • Structural basis of TSPAN8–MDM2 interaction not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of TSPAN8's multivalent scaffolding across integrins, receptors, and nuclear partners; whether the EGFR–AKT and AR-dependent nuclear import pathways converge or operate independently; the identity of the deubiquitinase(s) mediating mutual AR/TSPAN8 stabilization; and how TSPAN8 cargo-sorting specificity in exosomes is encoded.
  • No high-resolution structure of TSPAN8 in complex with any partner
  • No reconstitution of TSPAN8-dependent exosome sorting with purified components
  • Nuclear versus membrane pool regulation not mechanistically separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 7 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005634 nucleus 3 GO:0031410 cytoplasmic vesicle 3
Pathway
R-HSA-1643685 Disease 7 R-HSA-162582 Signal Transduction 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-1266738 Developmental Biology 1
Partners
ARATXN3CDH1CTNND1ITGA6ITGB4PTCH1STAT3
Complex memberships
TSPAN8–AR/AR-V7 complexTSPAN8–E-cadherin–p120-catenin complexTSPAN8–PTCH1–ATXN3 complexTSPAN8–integrin α6β4 complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 TSPAN8 (D6.1A, rat homologue of CO-029) associates with α6β1 integrin at the cell membrane, demonstrated by Western blotting of D6.1A-positive tumor lines, and transfection of D6.1A cDNA into a low-metastasizing tumor line increased metastatic potential accompanied by consumption coagulopathy. cDNA transfection, Western blotting, co-immunoprecipitation The Journal of cell biology Medium 9531564
2005 CO-029 (TSPAN8) co-localizes and co-immunoprecipitates with α6β4 integrin in human pancreatic adenocarcinoma cells; protein kinase C activation strengthens this association, leading to internalization of the integrin-tetraspanin complex, decreased laminin-5 adhesion, and increased cell migration. Co-immunoprecipitation, immunofluorescence colocalization, PKC activation assay, migration assay Clinical cancer research Medium 15837731
2006 CO-029/D6.1A (TSPAN8) expressed on tumor cells and their exosomes induces angiogenesis by stimulating MMP and uPA secretion, VEGF expression in fibroblasts, and VEGF receptor upregulation in sprouting endothelium; anti-D6.1A antibody completely blocked angiogenesis. In vivo angiogenesis assay, in vitro endothelial cell branching assay, antibody blocking, gene expression analysis Cancer research Medium 16849554
2010 Tspan8 selectively recruits proteins (including CD106 and CD49d) and mRNA into exosomes; exosomes bearing a Tspan8-CD49d complex preferentially bind and are internalized by endothelial cells, inducing VEGF-independent upregulation of angiogenesis-related genes and enhanced EC proliferation, migration, and sprouting. Exosome isolation and characterization, co-immunoprecipitation, gene expression profiling, EC functional assays Cancer research High 20124479
2010 Activation-induced Tspan8 internalization is faster than CD9 internalization and relies on association of the Tspan8 N-terminal region with intersectin-2 (a clathrin-coated pit component); PMA activation promotes recruitment of CD49d into a Tspan8-intersectin-2-CD49d-clathrin complex in cholesterol-depletion-resistant microdomains, promoting cell migration while reducing matrix and cell adhesion. Tspan8-chimera internalization assays, co-immunoprecipitation, cholesterol depletion, confocal microscopy, migration assays The international journal of biochemistry & cell biology Medium 20937409
2010 CO-029/Tspan8 directly interacts with E-cadherin (shown by chemical cross-linking and co-immunoprecipitation) and cooperates with p120-catenin to regulate colon carcinoma cell motility via a switch in signaling between collagen-binding integrins α1β1 and α2β1. Chemical cross-linking, co-immunoprecipitation, siRNA knockdown, migration assay, antibody blocking Cancer research High 20858717
2012 CO-029 (TSPAN8) knockdown in HT29 colon cancer cells reduces migration and increases integrin-dependent cell-matrix adhesion on laminin, upregulates cell surface levels of laminin-binding integrin α3β1 and α5β1, decreases CD44, and increases cadherin-mediated cell-cell adhesion while reducing MelCAM levels. siRNA knockdown, migration assay, flow cytometry for integrin surface levels, adhesion assay PloS one Medium 22679508
2013 Tspan8 knockdown in rat pancreatic adenocarcinoma ASML cells increases adhesion due to CD151 associating with α3 integrin; Tspan8 recruits β4 integrin into Tspan8 complexes with accompanying β4 phosphorylation, Src recruitment, FAK and Ras activation, driving motility over adhesion; CD151 associates more readily with MMP13 and MMP9 than Tspan8. Stable knockdown, co-immunoprecipitation, phosphorylation assays, signaling pathway analysis, invasion/migration assays European journal of cancer Medium 23683890
2015 Exosomal Tspan8 and CD151 support matrix degradation through tetraspanin-integrin and tetraspanin-protease associations; exosomes deficient in CD151/Tspan8 have reduced binding/uptake and fail to reprogram stroma, hematopoietic cells, or drive EMT gene expression in poorly metastatic cells. Stable knockdown, exosome isolation, functional reconstitution, co-immunoprecipitation Oncotarget Medium 25544774
2015 TM4SF3/TSPAN8 is localized not only to the plasma membrane but also to the nucleus of prostate cancer cells; this nuclear localization depends on androgen receptor (AR) nuclear localization. TM4SF3 directly interacts with AR, and this interaction stabilizes both proteins by reducing ubiquitin-proteasomal degradation; TM4SF3 is required for androgen-dependent gene expression and cancer cell proliferation. Co-immunoprecipitation, nuclear fractionation, immunofluorescence, siRNA knockdown, in vitro interaction assay, gene expression analysis Molecular endocrinology High 26649804
2015 LSD1 (histone demethylase) epigenetically upregulates TSPAN8 expression by reducing H3K9me2 occupancy on the TSPAN8 promoter in colorectal cancer cells; TSPAN8 promotes EMT in an LSD1-dependent manner. ChIP, siRNA knockdown, LSD1 inhibitor treatment, RT-PCR, Western blot, migration assay Life sciences Medium 31790687
2018 In Tspan8/CD151 knockout mice, impaired tumor dissemination is associated with distorted tetraspanin associations with integrins and CAM, and missing Tspan8/CD151-promoted recruitment of proteases; host Tspan8 in exosomes contributes to angiogenesis through association with GPCR and RTK in endothelial cells. Tspan8 knockout mice, tumor implantation, exosome coculture, co-immunoprecipitation, in vitro rescue experiments Journal of experimental & clinical cancer research High 30541597
2019 TSPAN8 interacts with PTCH1 and inhibits degradation of the SHH/PTCH1 complex by recruiting deubiquitinating enzyme ATXN3, thereby stabilizing the complex and enabling SMO translocation to cilia, activating downstream Hedgehog signaling and promoting cancer stem cell properties including NANOG/OCT4 expression and chemoresistance. Co-immunoprecipitation, ubiquitination assay, confocal microscopy (cilia localization), siRNA knockdown, in vivo tumor formation Nature communications High 31253779
2019 Tspan8 promotes breast cancer cell E-cadherin upregulation and Twist/p120-catenin/β-catenin target gene downregulation (resembling MET), and co-immunoprecipitation showed Tspan8 and p120-catenin interact; Tspan8 mediates a several-fold increase in extracellular vesicle numbers in cell culture and in vivo. Co-immunoprecipitation, EV quantification, Western blot, cell behavior assays The Journal of pathology Medium 30982971
2019 β-catenin stabilization occurs downstream of Tspan8 expression in melanoma; β-catenin in turn directly transcriptionally activates Tspan8, forming a positive feedback loop that sustains Tspan8-driven melanoma invasion. Tspan8 overexpression/knockdown, β-catenin reporter assay, ChIP, invasion assay, in vivo transgenic mouse model Oncogene Medium 30679790
2020 Tspan8+ melanoma cells cooperate with surrounding keratinocytes to activate keratinocyte-derived proMMP-9, degrade collagen IV, and achieve dermal colonization; this involves elevated MMP-3 and low TIMP-1 levels; anti-Tspan8 antibody reduces proMMP-9 activation and dermal invasion. 3D skin reconstruct model, MMP activity assay, antibody blocking, siRNA knockdown Cancers Medium 32455575
2022 EGFR signaling induces AKT-mediated phosphorylation of TSPAN8 at Ser129, enabling TSPAN8 binding to 14-3-3θ and importin-β1, which drives TSPAN8 nuclear translocation; in the nucleus, phosphorylated TSPAN8 interacts with STAT3 to enhance its chromatin occupancy and transcription of MYC, BCL2, MMP9 and other oncogenes. Co-immunoprecipitation, phospho-site mutagenesis, nuclear fractionation, ChIP, reporter assays, in vitro kinase assay, antibody blocking in vivo Cell research High 35197608
2023 TM4SF3/TSPAN8 physically interacts with AR-V7 (in addition to AR); interaction of TM4SF3 with AR or AR-V7 results in mutual deubiquitination and stabilization of both proteins; nuclear TM4SF3 is co-recruited to promoters of AR/AR-V7-regulated genes and is required for their transcriptional activation. Co-immunoprecipitation, ubiquitination assay, ChIP, nuclear fractionation, siRNA knockdown, domain mapping Endocrinology High 36951301
2023 Tspan8 coalesces with lipid rafts and facilitates IFN-γR1 localization at or near lipid rafts; Tspan8 silencing impairs lipid raft-mediated but promotes clathrin-mediated endocytosis of IFN-γR1, leading to increased STAT1 signaling and intestinal epithelial permeability. siRNA knockdown, lipid raft fractionation, endocytosis assay (clathrin vs lipid raft), STAT1 signaling readout, barrier permeability assay Cellular and molecular life sciences Medium 37204469
2023 Tspan8 associates with endothelin-converting enzyme ECE1 and amplifies its enzymatic activity in converting big-ET1 to endothelin-1, demonstrated by transduction of Tspan8 into Isreco1 cells and by comparing ileum tissue of tspan8 knockout vs. wild-type mice. Mass spectrometry, Western blot co-immunoprecipitation, ECE1 activity assay, tspan8 knockout mouse tissue comparison Cancers Medium 37835445
2024 TSPAN8 promotes phosphorylation of E3 ligase RBBP6 at Ser772 by recruiting MAPK11, inducing SIRT6 protein degradation; SIRT6 downregulation subsequently upregulates GLS1 and PYCR1, causing TSPAN8+ myofibroblastic CAFs to secrete aspartate and proline that support breast cancer cell outgrowth. Co-immunoprecipitation, phosphorylation assay, siRNA knockdown, SIRT6 activity assay, metabolite secretion measurement, in vivo xenograft Science translational medicine High 38569015
2024 MDM2 acts as the common E3 ubiquitin ligase for TM4SF3/TSPAN8, AR, and AR-V7; MDM2 inhibition elevated all three proteins by reducing their ubiquitination; TM4SF3 interaction with AR or AR-V7 results in mutual deubiquitination and prevents proteasomal degradation. siRNA depletion of E3 ligases, MDM2 pharmacological inhibitor, ubiquitination assay, protein stability assay Endocrine oncology Medium 38410785
2009 In Xenopus, tm4sf3 (TSPAN8 ortholog) is specifically expressed in the ventral pancreas at the fusion junction; morpholino-mediated knockdown inhibits dorsal-ventral pancreatic bud fusion and acinar cell differentiation, while overexpression promotes annular pancreas development. Morpholino knockdown, mRNA overexpression, Xenopus embryo model, in situ hybridization Development Medium 19403659
2021 TSPAN8-high spermatogonia in mouse testis are enriched for spermatogonial stem cells (SSCs), as demonstrated by transplantation studies showing that TSPAN8-high subpopulations have greater stem cell activity than TSPAN8-low progenitor spermatogonia. Flow cytometry cell sorting, spermatogonial transplantation assay, RNA-seq, ChIP-seq, Methyl-seq Biology of reproduction Medium 27733379
2021 TSPAN8 promotes cancer cell stemness by activating Sonic Hedgehog signaling through exosomal transfer; CSC-derived TSPAN8-enriched exosomes activate Hh signaling in non-stem cancer cells, increasing their clonogenic ability, invasiveness, and chemoresistance in PDAC. Single-cell RNA sequencing, exosomal profiling, functional assays (clonogenicity, invasion, chemoresistance), in vivo tumor growth Oncogene Medium 40251391
2019 TSPAN8 directly interacts with β-catenin (by Co-IP), enhances β-catenin protein expression, and promotes colorectal cancer stemness; β-catenin in turn directly binds the TSPAN8 promoter (by ChIP) and enhances TSPAN8 transcription, forming a positive regulatory loop. Co-immunoprecipitation, ChIP, siRNA knockdown, sphere formation assay, Western blot Medical science monitor Medium 31838484
2022 TSPAN8 forms a complex with Rictor (a component of mTORC2) and overexpression of TSPAN8 suppresses high-glucose-induced autophagy and apoptosis in kidney cells in an mTOR-dependent manner. Co-immunoprecipitation, TSPAN8 overexpression, mTOR inhibitor treatment, apoptosis/autophagy assays Cell biology international Low 35904232

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer research 545 20124479
2006 Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029. Cancer research 176 16849554
2019 TSPAN8 promotes cancer cell stemness via activation of sonic Hedgehog signaling. Nature communications 165 31253779
1990 Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens. Proceedings of the National Academy of Sciences of the United States of America 150 2395876
2015 The tetraspanins CD151 and Tspan8 are essential exosome components for the crosstalk between cancer initiating cells and their surrounding. Oncotarget 146 25544774
2008 Association testing of novel type 2 diabetes risk alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity, and obesity in a population-based sample of 4,516 glucose-tolerant middle-aged Danes. Diabetes 120 18567820
2005 Colocalization of the tetraspanins, CO-029 and CD151, with integrins in human pancreatic adenocarcinoma: impact on cell motility. Clinical cancer research : an official journal of the American Association for Cancer Research 109 15837731
1998 Association between the rat homologue of CO-029, a metastasis-associated tetraspanin molecule and consumption coagulopathy. The Journal of cell biology 89 9531564
2013 Tspan8, CD44v6 and alpha6beta4 are biomarkers of migrating pancreatic cancer-initiating cells. International journal of cancer 75 23338841
2024 TSPAN8+ myofibroblastic cancer-associated fibroblasts promote chemoresistance in patients with breast cancer. Science translational medicine 70 38569015
2010 E-cadherin/p120-catenin and tetraspanin Co-029 cooperate for cell motility control in human colon carcinoma. Cancer research 70 20858717
2001 Overexpression of tetraspanin CO-029 in hepatocellular carcinoma. Journal of hepatology 69 11690710
2010 Activation-induced internalization differs for the tetraspanins CD9 and Tspan8: Impact on tumor cell motility. The international journal of biochemistry & cell biology 67 20937409
2021 Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma. Nature communications 61 33674603
2022 EGFR signaling promotes nuclear translocation of plasma membrane protein TSPAN8 to enhance tumor progression via STAT3-mediated transcription. Cell research 59 35197608
2013 Tspan8 and CD151 promote metastasis by distinct mechanisms. European journal of cancer (Oxford, England : 1990) 57 23683890
2008 TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression. Clinical & experimental metastasis 53 18365756
2015 TSPAN8 promotes gastric cancer growth and metastasis via ERK MAPK pathway. International journal of clinical and experimental medicine 45 26309511
2021 SOX9 is a critical regulator of TSPAN8-mediated metastasis in pancreatic cancer. Oncogene 41 34163029
2003 Possible involvement of tetraspanin CO-029 in hematogenous intrahepatic metastasis of liver cancer cells. Journal of gastroenterology and hepatology 38 14535989
2019 Tspan8 is expressed in breast cancer and regulates E-cadherin/catenin signalling and metastasis accompanied by increased circulating extracellular vesicles. The Journal of pathology 37 30982971
2019 TSPAN8 promotes colorectal cancer cell growth and migration in LSD1-dependent manner. Life sciences 36 31790687
2014 Effect of an anti-human Co-029/tspan8 mouse monoclonal antibody on tumor growth in a nude mouse model. Frontiers in physiology 36 25285080
2018 Tspan8 and Tspan8/CD151 knockout mice unravel the contribution of tumor and host exosomes to tumor progression. Journal of experimental & clinical cancer research : CR 34 30541597
2016 TSPAN8 Expression Distinguishes Spermatogonial Stem Cells in the Prepubertal Mouse Testis. Biology of reproduction 32 27733379
2015 TSPAN8, identified by Escherichia coli ampicillin secretion trap, is associated with cell growth and invasion in gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 32 25711980
2009 The tetraspanin Tm4sf3 is localized to the ventral pancreas and regulates fusion of the dorsal and ventral pancreatic buds. Development (Cambridge, England) 31 19403659
2012 Tetraspanin CO-029 inhibits colorectal cancer cell movement by deregulating cell-matrix and cell-cell adhesions. PloS one 29 22679508
2018 MiR-324-5p reduces viability and induces apoptosis in gastric cancer cells through modulating TSPAN8. The Journal of pharmacy and pharmacology 28 30159900
2020 Colorectal cancer screening: Assessment of CEACAM6, LGALS4, TSPAN8 and COL1A2 as blood markers in faecal immunochemical test negative subjects. Journal of advanced research 26 32257432
2020 TSPAN8 as a Novel Emerging Therapeutic Target in Cancer for Monoclonal Antibody Therapy. Biomolecules 25 32138170
2010 Functional variants of TSPAN8 are associated with bipolar disorder and schizophrenia. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 25 20052686
2021 High TSPAN8 expression in epithelial cancer cell-derived small extracellular vesicles promote confined diffusion and pronounced uptake. Journal of extracellular vesicles 24 34796683
2010 Reduced body weight in male Tspan8-deficient mice. International journal of obesity (2005) 22 20733586
2019 Tspan8-β-catenin positive feedback loop promotes melanoma invasion. Oncogene 21 30679790
2015 Association of JAZF1 and TSPAN8/LGR5 variants in relation to type 2 diabetes mellitus in a Saudi population. Diabetology & metabolic syndrome 20 26500707
1989 Colon carcinoma-associated glycoproteins recognized by monoclonal antibodies CO-029 and GA22-2. Hybridoma 20 2777278
2020 Tspan8-Tumor Extracellular Vesicle-Induced Endothelial Cell and Fibroblast Remodeling Relies on the Target Cell-Selective Response. Cells 19 32013145
2015 Generation of a human antibody that inhibits TSPAN8-mediated invasion of metastatic colorectal cancer cells. Biochemical and biophysical research communications 19 26562525
2017 p53 targets TSPAN8 to prevent invasion in melanoma cells. Oncogenesis 18 28368391
2015 CO-029 is overexpressed in gastric cancer and mediates the effects of EGF on gastric cancer cell proliferation and invasion. International journal of molecular medicine 18 25592989
2020 Silencing of long non-coding RNA SOX21-AS1 inhibits lung adenocarcinoma invasion and migration by impairing TSPAN8 via transcription factor GATA6. International journal of biological macromolecules 17 32698071
2020 Tspan8 Drives Melanoma Dermal Invasion by Promoting ProMMP-9 Activation and Basement Membrane Proteolysis in a Keratinocyte-Dependent Manner. Cancers 16 32455575
2016 A large-scale RNAi screen identifies LCMR1 as a critical regulator of Tspan8-mediated melanoma invasion. Oncogene 16 27375018
2022 miR-543 regulates high glucose-induced fibrosis and autophagy in diabetic nephropathy by targeting TSPAN8. BMC nephrology 13 35246069
2021 SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator. bioRxiv : the preprint server for biology 12 34100012
2019 Comprehensive Genetic Search to Clarify the Molecular Mechanism of Drug Resistance Identifies ASCL2-LEF1/TSPAN8 Axis in Colorectal Cancer. Annals of surgical oncology 12 30706227
2017 Joint features and complementarities of Tspan8 and CD151 revealed in knockdown and knockout models. Biochemical Society transactions 11 28408484
2017 Multi-factorial modulation of colorectal carcinoma cells motility - partial coordination by the tetraspanin Co-029/tspan8. Oncotarget 11 28418857
2015 TM4SF3 and AR: A Nuclear Complex that Stabilizes Both Proteins. Molecular endocrinology (Baltimore, Md.) 11 26649804
2019 A Positive Tetraspanin 8 (TSPAN8)/β-Catenin Regulatory Loop Enhances the Stemness of Colorectal Cancer Cells. Medical science monitor : international medical journal of experimental and clinical research 10 31838484
2016 Overexpression of TSPAN8 Promotes Tumor Cell Viability and Proliferation in Nonsmall Cell Lung Cancer. Cancer biotherapy & radiopharmaceuticals 10 27996312
2024 Molecular Regulation and Oncogenic Functions of TSPAN8. Cells 8 38275818
2023 Tetraspanin Tspan8 restrains interferon signaling to stabilize intestinal epithelium by directing endocytosis of interferon receptor. Cellular and molecular life sciences : CMLS 7 37204469
2021 Signatures of TSPAN8 variants associated with human metabolic regulation and diseases. iScience 7 34401672
2017 HNF1B, TSPAN8 and NOTCH2 gene polymorphisms in women with gestational diabetes. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 7 28274157
2024 MDM2 regulates the stability of AR, AR-V7, and TM4SF3 proteins in prostate cancer. Endocrine oncology (Bristol, England) 5 38410785
2023 TSPAN8 regulates EGFR/AKT pathway to enhance metastasis in gastric cancer. Molecular biology reports 5 37535246
2022 TSPAN8 alleviates high glucose-induced apoptosis and autophagy via targeting mTORC2. Cell biology international 5 35904232
2022 Histone demethylase KDM2A suppresses EGF-TSPAN8 pathway to inhibit breast cancer cell migration and invasion in vitro. Biochemical and biophysical research communications 5 36084547
2023 The Transmembrane Protein TM4SF3 Interacts With AR and AR-V7 and is Recruited to AR Target Genes. Endocrinology 4 36951301
2024 Cancer Cell Biomechanical Properties Accompany Tspan8-Dependent Cutaneous Melanoma Invasion. Cancers 3 38398085
2024 Overexpression of TSPAN8 in consensus molecular subtype 3 colorectal cancer. Experimental and molecular pathology 3 38861838
2025 Cancer stem cells-derived exosomal TSPAN8 enhances non-stem cancer cells stemness and promotes malignant progression in PDAC. Oncogene 2 40251391
2023 The Tetraspanin Tspan8 Associates with Endothelin Converting Enzyme ECE1 and Regulates Its Activity. Cancers 2 37835445
2022 [TSPAN8 is involved in lipid metabolism in non-alcoholic fatty liver disease in mice]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 2 35673914
2025 Characterization of LINC00483 as a Novel Oncogene in Colorectal Cancer via Targeting miR-601/TSPAN8 Signaling Axis. Journal of biochemical and molecular toxicology 1 40059517
2024 miR-378a-5p represses Barrett's esophagus cells proliferation, migration and invasion through targeting TSPAN8. Cellular and molecular biology (Noisy-le-Grand, France) 0 38430035
2023 Regional expression differences of SERT and TSPAN8 in hippocampus, cerebellum and cortex of wild-type young, adult and middle-aged rats. Gene 0 37572802
2023 Peptides disrupting TM4SF3 interaction with AR or AR-V7 block prostate cancer cell proliferation. Endocrine oncology (Bristol, England) 0 37822366