ArticleJournal of experimental & clinical cancer research : CR2020
TM4SF1 promotes EMT and cancer stemness via the Wnt/β-catenin/SOX2 pathway in colorectal cancer.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 226 papers.
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Who cites it
226 citing papers in PubMed, 339 citations in OpenAlex.
- Colorectal cancer landscape from gut microbiota: Insights into mutations, epigenetic dysregulation, and immune microenvironment alterations.Virulence · 2026Review
- Gastrointestinal Microbiome Dysbiosis in Cancer Development: Mechanisms and Biomarker Potential.MicrobiologyOpen · 2026Review
- SOX2 Inhibits Cuproptosis to Affect Cisplatin Resistance in Non-Small Cell Lung Cancer by Activating the Wnt/ATP7B Signaling Pathway.The Kaohsiung journal of medical sciences · 2026Article
- Machine learning-based integration identifies a 10-gene predictive signature and its classification patterns in schizophrenia.European archives of psychiatry and clinical neuroscience · 2026Article
- Narciclasine Exerts Anticancer Activity in Colorectal Cancer Cells in Association with HELLS Downregulation and DNA Damage-Associated Responses.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Current Status of Intestinal Stem Cell Research: Mechanisms, Intestinal Diseases, and Organoid Development.Cells · 2026Review
- KIAA1429 Stabilizes FAM84B mRNA to Enhance Colorectal Cancer Tumorigenesis via Wnt/β-Catenin Pathway.Biochemical genetics · 2026Article
- [NPLOC4 promotes proliferation, invasion, and migration of hepatocellular carcinoma cells via enhancing Wnt/Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Article
- Mechanism of enteral nutrition in regulating Tfh/Tfr immune imbalance in colorectal cancer via the TLR4 signaling pathway.Journal of clinical biochemistry and nutrition · 2026Article
- Inhibition of the Metalloproteinase ADAMTS5 Suppresses Colorectal Cancer Metastasis via the PEDF/Wnt/β-Catenin Pathway.Cancer medicine · 2026Article
- Juglone targets CBS to inhibit the Wnt/β-catenin pathway and promotes osteosarcoma cell apoptosis.iScience · 2026Article
- NUP62 Elevates USP10 Expression and Promotes Tamoxifen Resistance of Breast Cancer by Deubiquitinating ERα.Annals of surgical oncology · 2026Article
- LRP2-mediated regulation of ferroptosis through the Wnt/β-catenin-GPX4 axis in colorectal cancer liver metastasis and chemoresistance.Cell death discovery · 2026Article
- NF-κB signaling in hepatocellular carcinoma: Mechanisms of tumor progression, immune evasion, and therapeutic resistance.Translational oncology · 2026Review
- A Hidden "Promoter":Infection and immunity · 2026Article
- SNHG5 enhances colorectal cancer metastasis through RNA-protein interaction with GNB2 and activation of canonical Wnt signaling.Non-coding RNA research · 2026Article
- Toward Computationally Complete Spatial Omics.bioRxiv : the preprint server for biology · 2026Article
- Engineered CAR-NKT Extracellular Vesicles Suppress Tumor Progression and Enhance Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Association between type 2 diabetes mellitus and colorectal adenoma: A retrospective study with insights into Wnt/β-Catenin/TCF7L2 pathway activation.World journal of gastrointestinal surgery · 2026Article
- Cross-cohort multi-omics analysis identifies novel clusters driven by epithelial-mesenchymal transition signatures in gastric cancer.Cancer cell international · 2026Article
166 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundTransmembrane 4 L six family member 1 (TM4SF1) is upregulated in several epithelial cancers and is closely associated with poor prognosis. However, the role of TM4SF1 and its potential mechanism in colorectal cancer (CRC) remain elusive.
methodsWe investigated the expression of TM4SF1 in the Oncomine, the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and confirmed the results by immunohistochemistry (IHC), qPCR and Western blotting (WB) of CRC tissues. The effect of TM4SF1 on the epithelial-to-mesenchymal transition (EMT) and cancer stemness of CRC cells was investigated by Transwell, wound healing and sphere formation assays. A series of in vitro and in vivo experiments were conducted to reveal the mechanisms by which TM4SF1 modulates EMT and cancer stemness in CRC.
resultsTM4SF1 expression was markedly higher in CRC tissues than in non-tumour tissues and was positively correlated with poor prognosis. Downregulation of TM4SF1 inhibited the migration, invasion and tumour sphere formation of SW480 and LoVo cells. Conversely, TM4SF1 overexpression significantly enhanced the migration, invasion and tumoursphere formation potential of CRC cells, Additionally, TM4SF1 silencing inhibited the EMT mediated by transforming growth factor-β1 (TGF-β1). Mechanistically, gene set enrichment analysis (GSEA) predicted that the Wnt signalling pathway was one of the most impaired pathways in TM4SF1-deficient CRC cells compared to controls. The results were further validated by WB, which revealed that TM4SF1 modulated SOX2 expression in a Wnt/β-catenin activation-dependent manner. Furthermore, we found that knockdown of TM4SF1 suppressed the expression of c-Myc, leading to decreased c-Myc binding to the SOX2 gene promoter. Finally, depletion of TM4SF1 inhibited metastasis and tumour growth in a xenograft mouse model.
conclusionOur study substantiates a novel mechanism by which TM4SF1 maintains cancer cell stemness and EMT via the Wnt/β-catenin/c-Myc/SOX2 axis during the recurrence and metastasis of CRC.
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