Affinage

TM4SF1

Transmembrane 4 L6 family member 1 · UniProt P30408

Length
202 aa
Mass
21.6 kDa
Annotated
2026-04-28
100 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TM4SF1 is a tetraspanin-like four-transmembrane glycoprotein that functions as a molecular organizer of membrane–cytoskeleton interactions to drive cell protrusion, polarization, migration, and invasion. On endothelial cells it localizes in a periodic banded pattern along filopodia and nanopodia, constitutively interacts with integrins α5/β1 (and conditionally with αV/β3/β5 upon VEGF-A or thrombin stimulation), and associates with myosin-10 and β-actin; knockdown abolishes nanopodia formation, blocks cytokinesis, induces senescence, and inhibits VEGF-A–driven angiogenesis in vivo (PMID:19351819, PMID:21626280). TM4SF1 resides in tetraspanin-enriched microdomains via its cytoplasmic domains, undergoes ubiquitylation required for pro-migratory function, and is internalized through a biosynthetic route to late endosomes (PMID:18270265). In cancer cells, TM4SF1 promotes invasion and metastasis by physically engaging DDR1 to sustain MMP2/MMP9 expression and invadopodia function, by interacting with DVL2 to activate Wnt/β-catenin signaling, and by coupling with integrin α6 to activate FAK-dependent migration (PMID:28368050, PMID:31876386, PMID:35835740).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1992 High

    Molecular cloning established TM4SF1 as a four-transmembrane surface glycoprotein with topology resembling the tetraspanin superfamily, providing the structural framework for all subsequent functional studies.

    Evidence Expression cloning in COS cells with antibody validation and hydropathy analysis

    PMID:1565644

    Open questions at the time
    • No function assigned beyond predicted membrane topology
    • Post-translational modifications not characterized
    • Binding partners unknown
  2. 2003 Medium

    Forced expression and antibody-clustering experiments demonstrated that TM4SF1 directly enhances tumor cell invasiveness and experimental metastasis, establishing it as a functionally pro-invasive membrane protein.

    Evidence TM4SF1 overexpression in lung carcinoma cells; Transwell invasion assays; SCID mouse metastasis model; antibody clustering

    PMID:12855661

    Open questions at the time
    • Downstream signaling pathways uncharacterized
    • Mechanism by which antibody clustering blocks invasion unknown
    • Endogenous loss-of-function data not yet available for cancer context
  3. 2008 High

    Subcellular trafficking and post-translational modification studies revealed that TM4SF1 is recruited to tetraspanin-enriched microdomains via its cytoplasmic domains, is ubiquitylated, and that both TERM association and ubiquitylation are required for its pro-migratory activity.

    Evidence Antibody internalization tracking, subcellular fractionation, domain-deletion mapping, ubiquitylation assays, and migration readouts in multiple cell lines

    PMID:18270265

    Open questions at the time
    • E3 ligase mediating TM4SF1 ubiquitylation not identified
    • Structural basis for TERM recruitment unknown
    • Relationship between late-endosomal targeting and signaling unclear
  4. 2009 High

    Identification of integrin partners and in vivo angiogenesis requirement showed that TM4SF1 constitutively binds integrins α5/β1, conditionally binds αV/β3/β5 upon VEGF-A or thrombin stimulation, and is essential for endothelial filopodia formation, cytokinesis, and VEGF-A–driven angiogenesis.

    Evidence Reciprocal co-immunoprecipitation; siRNA knockdown; live imaging; in vivo Matrigel angiogenesis assay

    PMID:19351819

    Open questions at the time
    • Direct versus indirect integrin interaction not resolved
    • How VEGF-A/thrombin remodel the TM4SF1 interactome mechanistically unknown
    • Cytokinesis failure mechanism not detailed
  5. 2011 High

    Discovery of nanopodia as TM4SF1-organized structures, together with identification of myosin-10 and β-actin as interaction partners, established TM4SF1 as a membrane–cytoskeleton organizer that initiates actin-based cell protrusions and polarized migration.

    Evidence Adenoviral overexpression; live-cell GFP imaging; electron microscopy; interaction proteomics (mass spectrometry); siRNA knockdown in endothelial cells and fibroblasts

    PMID:21626280

    Open questions at the time
    • Structural basis of periodic banding along nanopodia unresolved
    • Whether myosin-10 interaction is direct or via actin scaffolding unknown
    • In vivo nanopodia relevance beyond EC not demonstrated
  6. 2017 Medium

    In pancreatic cancer, TM4SF1 was shown to physically interact with DDR1 and to drive invadopodia formation via a TM4SF1→DDR1→MMP2/MMP9 axis, extending its role from endothelial protrusions to cancer cell invasion machinery.

    Evidence Co-immunoprecipitation; DDR1 rescue after TM4SF1 knockdown; gelatin degradation invadopodia assay

    PMID:28368050

    Open questions at the time
    • Whether DDR1 interaction is direct or bridged by integrins unclear
    • Not tested in non-pancreatic cancer contexts at the time
    • Collagen dependence of the TM4SF1–DDR1 axis not examined
  7. 2019 Medium

    Two studies expanded TM4SF1's signaling repertoire: interaction with DVL2 activates Wnt/β-catenin signaling in hepatocellular carcinoma, and TM4SF1-dependent DDR1 regulation was linked to Akt/ERK/mTOR signaling and chemoresistance in NSCLC.

    Evidence Co-immunoprecipitation of TM4SF1–DVL2; ubiquitination of β-catenin upon TM4SF1 knockdown; pathway inhibition in NSCLC cells

    PMID:31142317 PMID:31876386

    Open questions at the time
    • Direct binding interface between TM4SF1 and DVL2 not mapped
    • DDR1-Akt/ERK connection in NSCLC based on Western blot without interaction data
    • Whether Wnt activation and DDR1 regulation are independent or convergent pathways unknown
  8. 2020 Medium

    TM4SF1 was shown to drive EMT and cancer stemness in colorectal cancer through Wnt/β-catenin–dependent c-Myc activation, with c-Myc binding the SOX2 promoter, establishing a transcriptional mechanism linking TM4SF1 to stemness reprogramming.

    Evidence ChIP for c-Myc at SOX2 promoter; shRNA knockdown; sphere formation; xenograft model

    PMID:33153498

    Open questions at the time
    • How TM4SF1 activates Wnt/β-catenin upstream not mechanistically resolved
    • Direct versus indirect regulation of c-Myc/SOX2 not distinguished
    • Single cancer type examined
  9. 2022 Medium

    Identification of integrin α6 as a direct TM4SF1 partner and the TM4SF1/integrin α6/FAK axis as a driver of laminin-dependent migration and lung metastasis extended the integrin-partnership model beyond endothelial cells into epithelial cancer invasion.

    Evidence Co-immunoprecipitation; FAK inhibitor epistasis; laminin-coated Transwell assay; in vivo lung metastasis model in esophageal squamous cell carcinoma

    PMID:35835740

    Open questions at the time
    • Whether integrin α6 partnership is distinct from α5/β1 in a common complex unknown
    • Laminin isoform specificity not examined
    • Structural basis of TM4SF1–integrin interaction unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of TM4SF1's interactions with integrins and cytoskeletal partners, the identity of its E3 ubiquitin ligase, and the mechanism by which it selectively activates multiple signaling pathways in different cellular contexts remain unknown.
  • No atomic-resolution structure of TM4SF1 or any TM4SF1–partner complex
  • E3 ligase responsible for ubiquitylation not identified
  • Whether TM4SF1 functions as a passive scaffold or has intrinsic signaling activity unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 2 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1474244 Extracellular matrix organization 2 R-HSA-1500931 Cell-Cell communication 2
Partners
ACTBDDR1DVL2ITGA5ITGA6ITGB1ITGB3MYO10
Complex memberships
tetraspanin-enriched microdomains (TERM)

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 TM4SF1 (L6 antigen) was cloned and found to encode a ~24 kDa cell surface protein with three N-terminal hydrophobic transmembrane regions followed by a hydrophilic region with two potential N-linked glycosylation sites and a C-terminal hydrophobic transmembrane region, placing it in a family of proteins with similar predicted membrane topology implicated in cell growth. Expression cloning in COS cells; antibody reactivity; hydropathy/sequence analysis Proceedings of the National Academy of Sciences of the United States of America High 1565644
2009 TM4SF1 is highly expressed in endothelial cell filopodia in a banded pattern; TM4SF1 knockdown prevented filopodia formation, inhibited cell mobility, blocked cytokinesis, and caused EC senescence. Integrin-α5 and integrin-β1 interacted constitutively with TM4SF1, while integrin subunits αV, β3, and β5 interacted with TM4SF1 only after VEGF-A or thrombin stimulation. TM4SF1 knockdown substantially inhibited VEGF-A-induced angiogenesis in vivo. siRNA knockdown; immunostaining; co-immunoprecipitation; in vivo angiogenesis assay; live imaging Cancer research High 19351819
2011 TM4SF1 is necessary for the formation of unusually long, thin EC projections termed 'nanopodia'; TM4SF1 localizes in a regularly spaced banded pattern in nanopodia; overexpression drives nanopodia formation even in fibroblasts. Mass spectrometry demonstrated TM4SF1 interacts with myosin-10 and β-actin. TM4SF1 acts as a molecular organizer that interacts with membrane and cytoskeleton-associated proteins to initiate nanopodia and facilitate cell polarization and migration. Adenoviral transduction; live-cell GFP imaging; immunostaining (light and electron microscopy); mass spectrometry interaction proteomics; siRNA knockdown Angiogenesis High 21626280
2008 TM4SF1 (L6-Ag) is abundant on the plasma membrane and on intracellular vesicles co-localizing with late endosomal/lysosomal markers (Lamp1/Lamp2, LBPA); it is targeted to late endocytic organelles predominantly via a biosynthetic pathway. On the plasma membrane it is associated with tetraspanin-enriched microdomains (TERM); all three predicted cytoplasmic regions are required for effective recruitment to TERM. Recruitment to TERM correlates with pro-migratory activity. TM4SF1 is ubiquitylated, and ubiquitylation is essential for its function in cell migration. TM4SF1 depletion selectively reduces surface expression of tetraspanins CD63 and CD82. siRNA knockdown; antibody internalization; live-imaging; subcellular fractionation; domain mapping; ubiquitylation assay; surface expression analysis Journal of cell science High 18270265
2003 TM4SF1 (TAL6) expression correlates with in vitro invasiveness of lung carcinoma cell lines; forced TM4SF1 expression on CL1-0 cells significantly increased in vitro invasiveness and decreased survival in an experimental metastasis model. Antibody-mediated clustering of TM4SF1 on the cell surface was required for the anti-invasive effect of anti-L6 antibody. Forced overexpression; Transwell invasion assay; SCID mouse experimental metastasis model; antibody clustering experiment Clinical cancer research Medium 12855661
2017 TM4SF1 co-localizes with DDR1 and physically interacts with DDR1 in pancreatic cancer cells; TM4SF1 silencing reduces DDR1 expression, impairs invadopodia formation and function, and decreases MMP2 and MMP9 expression; restoring DDR1 expression rescues these defects, establishing a TM4SF1→DDR1→MMP2/MMP9 axis promoting invadopodia-mediated invasion. Co-immunoprecipitation; double fluorescence immunostaining; siRNA knockdown; DDR1 rescue experiments; gelatin degradation invadopodia assay Scientific reports Medium 28368050
2020 TM4SF1 promotes EMT and cancer stemness in colorectal cancer via the Wnt/β-catenin/c-Myc/SOX2 axis; TM4SF1 knockdown suppresses Wnt/β-catenin activation and reduces c-Myc binding to the SOX2 promoter; TM4SF1 modulates SOX2 expression in a Wnt/β-catenin-dependent manner. siRNA/shRNA knockdown; GSEA pathway analysis; Western blotting; chromatin immunoprecipitation (c-Myc binding to SOX2 promoter); xenograft mouse model; sphere formation assay Journal of experimental & clinical cancer research Medium 33153498
2019 TM4SF1 promotes NSCLC proliferation, invasion, and chemo-resistance by regulating DDR1 expression and its downstream Akt/ERK/mTOR pathway; TM4SF1 silencing induced G2/M arrest and apoptosis, and sensitized cells to cisplatin and paclitaxel. siRNA knockdown; Western blotting; flow cytometry; MTS/clonogenic assay; Transwell assay Respiratory research Medium 31142317
2019 TM4SF1 physically interacts with DVL2 in hepatocellular carcinoma cells, strengthening the DVL2-Axin interaction and thereby activating Wnt/β-catenin signaling; TM4SF1 knockdown promotes β-catenin ubiquitination and reduces Axin2 and cyclin D1 expression. Co-immunoprecipitation; Western blotting; siRNA knockdown; ubiquitination assay; reporter gene assay Journal of cellular and molecular medicine Medium 31876386
2022 TM4SF1 promotes esophageal squamous cell carcinoma cell adhesion, spreading, migration, and invasion in a laminin-dependent manner by directly interacting with integrin α6; the TM4SF1/integrin α6/FAK signaling axis mediates cell migration; inhibiting FAK or knocking down TM4SF1 attenuates migration and lung metastasis. Co-immunoprecipitation; siRNA knockdown; FAK inhibitor treatment; laminin-coated Transwell assay; in vivo lung metastasis model Cell death & disease Medium 35835740
2015 TM4SF1 is internalized upon antibody binding; anti-TM4SF1 antibody-drug conjugates selectively kill TM4SF1-expressing tumor and endothelial cells in vitro and induce tumor regression in vivo, demonstrating that antibody-induced internalization of TM4SF1 is sufficient to deliver cytotoxic payload intracellularly. ADC internalization assay; cell viability assay; xenograft mouse tumor models Molecular cancer therapeutics Medium 26089370
2017 TM4SF1 regulates apoptosis, cell cycle progression, and ROS metabolism in bladder cancer cells via the PPARγ-SIRT1 feedback loop; knockdown of TM4SF1 upregulates ROS, induces cell cycle arrest and apoptosis, and these effects are reversed by the PPARγ antagonist GW9662 or the SIRT1 activator resveratrol. siRNA knockdown; flow cytometry (cell cycle and apoptosis); ROS measurement; pharmacological rescue with GW9662 and resveratrol; xenograft model Cancer letters Low 29175458
2023 TM4SF1 upregulates MYH9, which in turn activates the NOTCH pathway, promoting cancer stemness and lenvatinib resistance in hepatocellular carcinoma; protein mass spectrometry identified MYH9 as a downstream interactor of TM4SF1. Protein mass spectrometry; bioinformatics; Western blotting; in vitro and in vivo functional assays; lenvatinib-resistant cell line generation Biology direct Low 37069693
2021 B7-H3 prevents DOX-induced cellular senescence through the AKT/TM4SF1/SIRT1 pathway in colorectal cancer; blocking TM4SF1 (downstream of AKT) reverses B7-H3-mediated resistance to senescence, positioning TM4SF1 as an effector in this anti-senescence signaling cascade. RNA-seq; Western blotting; pathway inhibition experiments; siRNA knockdown; senescence assay; in vivo xenograft Cell death & disease Low 33958586

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Protein kinase B/Akt participates in GLUT4 translocation by insulin in L6 myoblasts. Molecular and cellular biology 498 10330141
2007 Lactate sensitive transcription factor network in L6 cells: activation of MCT1 and mitochondrial biogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 347 17395833
2020 TM4SF1 promotes EMT and cancer stemness via the Wnt/β-catenin/SOX2 pathway in colorectal cancer. Journal of experimental & clinical cancer research : CR 275 33153498
2000 Insulin-induced actin filament remodeling colocalizes actin with phosphatidylinositol 3-kinase and GLUT4 in L6 myotubes. Journal of cell science 184 10633079
2003 Raising Ca2+ in L6 myotubes mimics effects of exercise on mitochondrial biogenesis in muscle. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 177 12665481
1992 Development regulation of the subcellular distribution and glycosylation of GLUT1 and GLUT4 glucose transporters during myogenesis of L6 muscle cells. The Journal of biological chemistry 151 1311324
2008 Dexamethasone and corticosterone induce similar, but not identical, muscle wasting responses in cultured L6 and C2C12 myotubes. Journal of cellular biochemistry 147 18615595
1991 Differential expression of the GLUT1 and GLUT4 glucose transporters during differentiation of L6 muscle cells. Biochemical and biophysical research communications 138 2018509
1992 Cloning and expression of the tumor-associated antigen L6. Proceedings of the National Academy of Sciences of the United States of America 134 1565644
2001 Protein-tyrosine phosphatase-1B negatively regulates insulin signaling in l6 myocytes and Fao hepatoma cells. The Journal of biological chemistry 124 11136729
2002 Sustained exposure of L6 myotubes to high glucose and insulin decreases insulin-stimulated GLUT4 translocation but upregulates GLUT4 activity. Diabetes 114 12086937
2001 Troglitazone induces GLUT4 translocation in L6 myotubes. Diabetes 111 11334413
2005 Regulation of fatty acid uptake and metabolism in L6 skeletal muscle cells by resistin. FEBS letters 98 16137686
1999 GLUT-4myc ectopic expression in L6 myoblasts generates a GLUT-4-specific pool conferring insulin sensitivity. The American journal of physiology 92 10484371
1998 GLP-1 action in L6 myotubes is via a receptor different from the pancreatic GLP-1 receptor. The American journal of physiology 88 9730951
1998 Dexamethasone stimulates proteasome- and calcium-dependent proteolysis in cultured L6 myotubes. Shock (Augusta, Ga.) 88 9788663
2009 The L6 protein TM4SF1 is critical for endothelial cell function and tumor angiogenesis. Cancer research 83 19351819
1992 Pharmacological characterization of a receptor for calcitonin gene-related peptide on rat, L6 myocytes. British journal of pharmacology 77 1313730
1986 The development of insulin receptors and responsiveness is an early marker of differentiation in the muscle cell line L6. Endocrinology 76 3510122
2003 Tumor-associated antigen L6 and the invasion of human lung cancer cells. Clinical cancer research : an official journal of the American Association for Cancer Research 74 12855661
1999 Analysis of alternative transcripts of the flax L6 rust resistance gene. The Plant journal : for cell and molecular biology 70 10097386
2017 TM4SF1 regulates apoptosis, cell cycle and ROS metabolism via the PPARγ-SIRT1 feedback loop in human bladder cancer cells. Cancer letters 68 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
2012 Quercetin decreases inflammatory response and increases insulin action in skeletal muscle of ob/ob mice and in L6 myotubes. European journal of pharmacology 61 22713545
2016 TM4SF1 Promotes Proliferation, Invasion, and Metastasis in Human Liver Cancer Cells. International journal of molecular sciences 57 27153056
2013 Regulation of the HDM2-p53 pathway by ribosomal protein L6 in response to ribosomal stress. Nucleic acids research 56 24174547
2008 The tumour-associated antigen L6 (L6-Ag) is recruited to the tetraspanin-enriched microdomains: implication for tumour cell motility. Journal of cell science 55 18270265
2000 Glucocorticoids abate p70(S6k) and eIF4E function in L6 skeletal myoblasts. American journal of physiology. Endocrinology and metabolism 55 10893325
2009 Cyclic stretch reduces myofibrillar protein synthesis despite increases in FAK and anabolic signalling in L6 cells. The Journal of physiology 54 19470773
2018 MiRNA-206 suppresses PGE2-induced colorectal cancer cell proliferation, migration, and invasion by targetting TM4SF1. Bioscience reports 53 30135139
2011 TM4SF1: a tetraspanin-like protein necessary for nanopodia formation and endothelial cell migration. Angiogenesis 53 21626280
2014 Identifying Neisseria species by use of the 50S ribosomal protein L6 (rplF) gene. Journal of clinical microbiology 52 24523465
2009 Oleate protects against palmitate-induced insulin resistance in L6 myotubes. The British journal of nutrition 52 19622194
1994 The biologic window for chimeric L6 radioimmunotherapy. Cancer 52 8306244
2004 Depletion of mitochondrial DNA causes impaired glucose utilization and insulin resistance in L6 GLUT4myc myocytes. The Journal of biological chemistry 51 15764607
2005 Regulation of multidrug resistance by ribosomal protein l6 in gastric cancer cells. Cancer biology & therapy 50 15846068
2001 C-peptide attenuates protein tyrosine phosphatase activity and enhances glycogen synthesis in L6 myoblasts. Biochemical and biophysical research communications 49 11162564
2006 Protein kinase Czeta mediates insulin-induced glucose transport through actin remodeling in L6 muscle cells. Molecular biology of the cell 48 16525020
2005 Quantification of hormone-induced atrophy of large myotubes from C2C12 and L6 cells: atrophy-inducible and atrophy-resistant C2C12 myotubes. American journal of physiology. Cell physiology 48 16176969
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
2009 Genistein-derivatives from Tetracera scandens stimulate glucose-uptake in L6 myotubes. Biological & pharmaceutical bulletin 46 19252305
1993 Glucose transport in L6 myoblasts overexpressing GLUT1 and GLUT4. The Journal of biological chemistry 46 8408071
1997 Glucose transporter expression in L6 muscle cells: regulation through insulin- and stress-activated pathways. The American journal of physiology 44 9252481
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 43 31142317
2009 Possible mechanisms underlying statin-induced skeletal muscle toxicity in L6 fibroblasts and in rats. Journal of pharmacological sciences 43 19129682
2007 Protein arginine methylation regulates insulin signaling in L6 skeletal muscle cells. Biochemical and biophysical research communications 43 17971302
2015 Novel Anti-TM4SF1 Antibody-Drug Conjugates with Activity against Tumor Cells and Tumor Vasculature. Molecular cancer therapeutics 40 26089370
1996 A rat skeletal muscle cell line (L6) expresses specific adrenomedullin binding sites but activates adenylate cyclase via calcitonin gene-related peptide receptors. The Biochemical journal 40 8761478
2015 TM4SF1 Promotes Gemcitabine Resistance of Pancreatic Cancer In Vitro and In Vivo. PloS one 39 26709920
2009 USP19-deubiquitinating enzyme regulates levels of major myofibrillar proteins in L6 muscle cells. American journal of physiology. Endocrinology and metabolism 39 19773579
1984 Manipulation of medium conditions and differentiation in the rat myogenic cell line L6. Developmental biology 38 6706000
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
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
1989 Elevated c-fos expression inhibits differentiation of L6 rat myoblasts. Journal of cellular physiology 35 2469685
1984 Preferential use of A- and U-rich codons for Mycoplasma capricolum ribosomal proteins S8 and L6. Nucleic acids research 34 6095194
2021 B7-H3 suppresses doxorubicin-induced senescence-like growth arrest in colorectal cancer through the AKT/TM4SF1/SIRT1 pathway. Cell death & disease 33 33958586
2015 Fructose-induced ROS generation impairs glucose utilization in L6 skeletal muscle cells. Free radical research 33 25968943
2017 Effects of DEHP and its metabolite MEHP on insulin signalling and proteins involved in GLUT4 translocation in cultured L6 myotubes. Toxicology 32 28526321
2011 The L6 domain tetraspanin Tm4sf4 regulates endocrine pancreas differentiation and directed cell migration. Development (Cambridge, England) 32 21750032
2023 TM4SF1 upregulates MYH9 to activate the NOTCH pathway to promote cancer stemness and lenvatinib resistance in HCC. Biology direct 31 37069693
1999 Involvement of type 4 cAMP-phosphodiesterase in the myogenic differentiation of L6 cells. Molecular biology of the cell 30 10588663
2019 Robust intrinsic differences in mitochondrial respiration and H2O2 emission between L6 and C2C12 cells. American journal of physiology. Cell physiology 29 31091142
2019 Neferine Promotes GLUT4 Expression and Fusion With the Plasma Membrane to Induce Glucose Uptake in L6 Cells. Frontiers in pharmacology 29 31551792
2013 Antihyperglycemic effect of equol, a daidzein derivative, in cultured L6 myocytes and ob/ob mice. Molecular nutrition & food research 29 24039053
2012 Astragalus polysaccharide stimulates glucose uptake in L6 myotubes through AMPK activation and AS160/TBC1D4 phosphorylation. Acta pharmacologica Sinica 29 23103623
2014 Functional interaction between ribosomal protein L6 and RbgA during ribosome assembly. PLoS genetics 28 25330043
1990 Effect of GTP gamma S on insulin binding and tyrosine phosphorylation in liver membranes and L6 muscle cells. The American journal of physiology 28 2105654
2007 TNF-alpha and glucocorticoid receptor interaction in L6 muscle cells: a cooperative downregulation of myosin heavy chain. Steroids 27 17624386
1986 Myoglobin expression in L6 muscle cells. Role of differentiation and heme. The Journal of biological chemistry 27 3722191
2018 Puerarin attenuates palmitate-induced mitochondrial dysfunction, impaired mitophagy and inflammation in L6 myotubes. Life sciences 26 29802940
1998 Intracellular association of FGF-2 with the ribosomal protein L6/TAXREB107. Biochemical and biophysical research communications 26 9826564
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
2015 Molecular evidence of insulinomimetic property exhibited by steviol and stevioside in diabetes induced L6 and 3T3L1 cells. Phytomedicine : international journal of phytotherapy and phytopharmacology 24 26407946
2009 Hypoxia alters contractile protein homeostasis in L6 myotubes. FEBS letters 24 19364505
2004 Signalling mechanisms underlying the rapid and additive stimulation of NKCC activity by insulin and hypertonicity in rat L6 skeletal muscle cells. The Journal of physiology 24 15284343
1999 Interaction of the sarcin/ricin domain of 23 S ribosomal RNA with proteins L3 and L6. The Journal of biological chemistry 24 9873002
2019 TM4SF1 is a potential target for anti-invasion and metastasis in ovarian cancer. BMC cancer 23 30876464
2003 Integrin-linked kinase is a positive mediator of L6 myoblast differentiation. Biochemical and biophysical research communications 23 14550274
1992 Expression and turnover of acylphosphatase (muscular isoenzyme) in L6 myoblasts during myogenesis. Archives of biochemistry and biophysics 23 1312807
2021 Constitutive expression of Ribosomal Protein L6 modulates salt tolerance in rice transgenic plants. Gene 22 33892070
2019 TM4SF1, a binding protein of DVL2 in hepatocellular carcinoma, positively regulates beta-catenin/TCF signalling. Journal of cellular and molecular medicine 22 31876386
1996 Regulation of calcium binding proteins calreticulin and calsequestrin during differentiation in the myogenic cell line L6. Journal of cellular physiology 22 8600158
1995 Retinoic acid stimulates glucose transporter expression in L6 muscle cells. Molecular and cellular endocrinology 22 7758830
2016 Involvement of ribosomal protein L6 in assembly of functional 50S ribosomal subunit in Escherichia coli cells. Biochemical and biophysical research communications 21 27003253
2014 Thyroid hormone inhibition in L6 myoblasts of IGF-I-mediated glucose uptake and proliferation: new roles for integrin αvβ3. American journal of physiology. Cell physiology 21 24808494
1994 Endothelin mobilizes calcium and enhances glucose uptake in cultured human skeletal myoblasts and L6 myotubes. Hypertension (Dallas, Tex. : 1979) 21 7515852
2023 TM4SF1-AS1 inhibits apoptosis by promoting stress granule formation in cancer cells. Cell death & disease 20 37443145
2022 TM4SF1 promotes esophageal squamous cell carcinoma metastasis by interacting with integrin α6. Cell death & disease 20 35835740
2018 Clinical significance of TM4SF1 as a tumor suppressor gene in gastric cancer. Cancer medicine 20 29665316
2012 Honokiol and magnolol stimulate glucose uptake by activating PI3K-dependent Akt in L6 myotubes. BioFactors (Oxford, England) 20 22674833
2001 Heat shock protects L6 myotubes from catabolic effects of dexamethasone and prevents downregulation of NF-kappaB. American journal of physiology. Regulatory, integrative and comparative physiology 20 11557628
2000 The human ribosomal protein L6 gene in a critical region for Noonan syndrome. Journal of human genetics 20 11043511
2018 microRNA-520f inhibits hepatocellular carcinoma cell proliferation and invasion by targeting TM4SF1. Gene 19 29505836
2017 TM4SF1 promotes the self-renewal of esophageal cancer stem-like cells and is regulated by miR-141. Oncotarget 19 27974706
2013 Impact of GLO1 knock down on GLUT4 trafficking and glucose uptake in L6 myoblasts. PloS one 18 23717693
2008 Pharmacological manipulation of L-carnitine transport into L6 cells with stable overexpression of human OCTN2. Cellular and molecular life sciences : CMLS 18 18408886
1996 Costimulation by CD28 sFv expressed on the tumor cell surface or as a soluble bispecific molecule targeted to the L6 carcinoma antigen. Tissue antigens 18 8946677
2016 INVOLVEMENT OF PEPTIDOGLYCAN RECOGNITION PROTEIN L6 IN ACTIVATION OF IMMUNE DEFICIENCY PATHWAY IN THE IMMUNE RESPONSIVE SILKWORM CELLS. Archives of insect biochemistry and physiology 17 26991439