ArticleCancer science2013
SOX2 promotes tumor growth of esophageal squamous cell carcinoma through the AKT/mammalian target of rapamycin complex 1 signaling pathway.
Article in Cancer science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 72 citations in OpenAlex.
- Phaeochromocytomas and paragangliomas harbour tumour-initiating SOX2+ stem cells.Endocrine-related cancer · 2026Article
- Article
- Control of SOX2 protein stability and tumorigenic activity by E3 ligase CHIP in esophageal cancer cells.Oncogene · 2023Article
- GSK3β-driven SOX2 overexpression is a targetable vulnerability in esophageal squamous cell carcinoma.Oncogene · 2023Article
- Roles of oncogenes in esophageal squamous cell carcinoma and their therapeutic potentials.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Potent molecular-targeted therapies for advanced esophageal squamous cell carcinoma.Therapeutic advances in medical oncology · 2023Review
- SOX2 inhibits LLGL2 polarity protein in esophageal squamous cell carcinoma via miRNA-142-3p.Cancer biology & therapy · 2022Article
- Downregulation of TUSC3 promotes EMT and hepatocellular carcinoma progression through LIPC/AKT axis.Journal of translational medicine · 2022Article
- Exploiting the Molecular Basis of Oesophageal Cancer for Targeted Therapies and Biomarkers for Drug Response: Guiding Clinical Decision-Making.Biomedicines · 2022Review
- Identifying a confused cell identity for esophageal squamous cell carcinoma.Signal transduction and targeted therapy · 2022Article
- Review
- TUSC3 inhibits cell proliferation and invasion in cervical squamous cell carcinoma via suppression of the AKT signalling pathway.Journal of cellular and molecular medicine · 2022Article
- PI3K/Akt/mTOR Signaling Pathway: Role in Esophageal Squamous Cell Carcinoma, Regulatory Mechanisms and Opportunities for Targeted Therapy.Frontiers in oncology · 2022Review
- SOX2 enhances cell survival and induces resistance to apoptosis under serum starvation conditions through the AKT/GSK-3β signaling pathway in esophageal squamous cell carcinoma.Oncology letters · 2021Article
- SOX2-Upregulated microRNA-30e Promotes the Progression of Esophageal Cancer via Regulation of the USP4/SMAD4/CK2 Axis.Molecular therapy. Nucleic acids · 2021Article
- Melanoma stem cell maintenance and chemo-resistance are mediated by CD133 signal to PI3K-dependent pathways.Oncogene · 2020Article
- Functional characterization of SOX2 as an anticancer target.Signal transduction and targeted therapy · 2020Review
- Heterogeneous genomic aberrations in esophageal squamous cell carcinoma: a review.American journal of translational research · 2020Review
- SOX2 protein biochemistry in stemness, reprogramming, and cancer: the PI3K/AKT/SOX2 axis and beyond.Oncogene · 2020Review
- SOX2 antagonizes WWC1 to drive YAP1 activation in esophageal squamous cell carcinoma.Cancer medicine · 2019Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor SOX2 is essential for the maintenance of embryonic stem cells and normal development of the esophagus. Our previous study revealed that the SOX2 gene is an amplification target of 3q26.3 in esophageal squamous cell carcinoma (ESCC), and that SOX2 promotes ESCC cell proliferation in vitro. In the present study, we aimed to identify the mechanisms by which SOX2 promotes proliferation of ESCC cells. Using a phosphoprotein array, we assayed multiple signaling pathways activated by SOX2 and determined that SOX2 activated the AKT/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. LY294002, an inhibitor of phosphatidylinositol 3-kinase, and rapamycin, an inhibitor of mTORC1, suppressed the ability of SOX2 to enhance proliferation of ESCC cells in vitro. Effects of SOX2 knockdown, including reduced levels of phosphorylated AKT and decreased ESCC cell proliferation, were reversed with constitutive activation of AKT with knockdown of phosphatase and tensin homolog. In mouse xenografts, SOX2 promoted in vivo tumor growth of ESCC, which was dependent on AKT/mTORC1 activation. LY294002 suppressed the ability of SOX2 to enhance tumor growth of ESCC by reducing cell proliferation, but not by enhancing apoptosis. Furthermore, tissue microarray analysis of 61 primary ESCC tumors showed a positive correlation between expression levels of SOX2 and phosphorylated AKT. Our findings suggest that SOX2 promotes in vivo tumor growth of ESCC through activation of the AKT/mTORC1 signaling pathway, which enhances cell proliferation.
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