ArticleEBioMedicine2019
Targeting cancer stem cell signature gene SMOC-2 Overcomes chemoresistance and inhibits cell proliferation of endometrial carcinoma.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Pooled it
- A Metabolic-Epigenetic Axis of AARS1/IGF2BP3-K280 Lactylation Sustains Endometrial Cancer Stemness and Recurrence.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SMOC2 promotes partial epithelial-mesenchymal transition and maladaptive repair in renal tubular epithelial cells.JCI insight · 2026Article
- SPARC family proteins: matricellular modulators of cancer progression and therapeutic resistance.Cancer gene therapy · 2026Review
- The inwardly rectifying potassium channel KCNJ12 regulates the stemness of hepatocellular carcinoma cells through the Wnt/β-catenin pathway.Journal of molecular cell biology · 2026Article
- DNA base lesion-containing G-quadruplex mediates transcriptome reprogramming in EGFR-TKI resistance of non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Matricellular protein SMOC2 safeguards tubular integrity in acute kidney injury via integrin β3-dependent inhibition of CCND1-CDK4/6 axis.Molecular biomedicine · 2026Article
- Regulation of Histone Emulsification by HPDL via LDHA/LDHB Promotes EC Cell Proliferation.Oncology research · 2026Article
- SMOC2 promotes peritoneal metastasis of gastric cancer involving Wnt/β-catenin pathway modulation and inducing angiogenesis.Clinical and experimental medicine · 2025Article
- EGFR controls transcriptional and metabolic rewiring in KRASEMBO molecular medicine · 2025Article
- Single-cell transcriptome analysis identifies subclusters and signature with N-glycosylation in endometrial cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- The Importance of Cancer Stem Cells and Their Pathways in Endometrial Cancer: A Narrative Review.Cells · 2025Review
- From Synthesis to Solutions: Hydrogels' Impact on the Biomedical Landscape.Current pharmaceutical biotechnology · 2025Review
- Novel targets and their functions in the prognosis of uterine corpus endometrial cancer patients.Journal of applied genetics · 2024Article
- WTAP/IGF2BP3 mediated m6A modification of the EGR1/PTEN axis regulates the malignant phenotypes of endometrial cancer stem cells.Journal of experimental & clinical cancer research : CR · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- The Endometrial Stem/Progenitor Cells and Their Niches.Stem cell reviews and reports · 2024Review
- Stem cell index-based RiskScore model for predicting prognosis in thyroid cancer and experimental verification.Heliyon · 2024Article
- Review
- Targeting PUF60 prevents tumor progression by retarding mRNA decay of oxidative phosphorylation in ovarian cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEndometrial cancer is one of the most common gynecological malignancies and has exhibited an increasing incidence rate in recent years. Cancer stem cells (CSCs), which are responsible for tumor growth and chemoresistance, have been confirmed in endometrial cancer. However, it is still challenging to identify endometrial cancer stem cells to then target for therapy.
methodsFlow cytometry was used to identify the endometrial cancer stem cells. Sphere formation assay, western blotting, qRT-PCR assay, cell viability assay, xenograft assay and immunohistochemistry staining analysis were utilized to evaluate the effect of SPARC-related modular calcium binding 2 (SMOC-2) on the cells proliferation and drug resistance. Cell viability assay, qRT-PCR assay, immunofluorescence staining, Co-IP assay and luciferase reporter gene assay were performed to explore the possible molecular mechanism by which SMOC-2 activates WNT/β-catenin pathway.
findingsWe found the expression of SPARC-related modular calcium binding 2 (SMOC-2), a member of SPARC family, was higher in endometrial CSCs than that in non-CSCs. SMOC-2 was also more highly expressed in spheres than in monolayer cultures. The silencing of SMOC-2 suppressed cell sphere ability; reduced the expression of the stemness-associated genes SOX2, OCT4 and NANOG; and enhanced chemosensitivity in endometrial cancer cells. By co-culture IP assay, we demonstrated that SMOC-2 directly interacted with WNT receptors (Fzd6 and LRP6), enhanced ligand-receptor interaction with canonical WNT ligands (Wnt3a and Wnt10b), and finally, activated the WNT/β-catenin pathway in endometrial cancer. SMOC-2 expression was closely correlated with CSC markers CD133 and CD44 expression in endometrial cancer tissue.
interpretationTaken together, we conclude that SMOC-2 might be a novel endometrial cancer stem cell signature gene and therapeutic target for endometrial cancer. FUND: National Natural Science Foundation of China, Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission, Scientific and Technological Innovation Act Program of Fengxian Science and Technology Commission, Natural Science Foundation of Shanghai.
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