ArticleOncogene2019
AKT drives SOX2 overexpression and cancer cell stemness in esophageal cancer by protecting SOX2 from UBR5-mediated degradation.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 103 citations in OpenAlex.
- A bibliometric analysis of post-translational modifications in esophageal cancer based on the Web of Science Core Collection database [2000-2026].Journal of thoracic disease · 2026Article
- Sox2 protein stability is enhanced by BRafV600E and Pten deletion in adult neural stem/progenitor cells.NPJ precision oncology · 2026Article
- Article
- Switching of the c-Myc protein degradation pathway depending on the PP2A-B55α complex levels.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- SOX2 drives esophageal squamous carcinoma by reprogramming lipid metabolism and histone acetylation landscape.Nature communications · 2025Article
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- AKT1 as a therapeutic target for platinum-resistant SOX2 positive ovarian cancer cells.Scientific reports · 2025Article
- Targeting AKT as a promising strategy for SOX2-positive, chemoresistant osteosarcoma.Bone research · 2025Article
- Protocatechualdehyde Induced Breast Cancer Stem Cell Death via the Akt/Sox2 Signaling Pathway.International journal of molecular sciences · 2025Article
- FDFT1 maintains glioblastoma stem cells through activation of the Akt pathway.Stem cell research & therapy · 2024Article
- Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Research advancements on the involvement of E3 ubiquitin ligase UBR5 in gastrointestinal cancers.Heliyon · 2024Review
- Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.International journal of molecular sciences · 2024Review
- SF3A2 promotes progression and cisplatin resistance in triple-negative breast cancer via alternative splicing of MKRN1.Science advances · 2024Article
- LncRNA linc01194 promotes the progress of endometrial carcinoma by up-regulating SOX2 through binding to IGF2BP1.Journal of gynecologic oncology · 2024Article
- Article
- GSK3β-driven SOX2 overexpression is a targetable vulnerability in esophageal squamous cell carcinoma.Oncogene · 2023Article
- MLL4 Regulates the Progression of Non-Small-Cell Lung Cancer by Regulating the PI3K/AKT/SOX2 Axis.Cancer research and treatment · 2023Article
- Genome-wide CRISPR knockout screening identified G protein pathway suppressor 2 as a novel tumor suppressor for uveal melanoma metastasis.Journal of cancer research and clinical oncology · 2023Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a transcription factor critical for embryonic and adult stem cell self-renewal and function, SOX2 gene amplification has been recognized as a driving factor for various cancers including esophageal cancer. SOX2 overexpression occurs more broadly in cancer than gene amplification, but the mechanism is poorly understood. Here we showed that in esophageal cancer cell lines the levels of SOX2 proteins are not directly correlated to the copy numbers of SOX2 genes and are strongly influenced by proteostasis. We showed that AKT is a major determinant for SOX2 overexpression and does so by protecting SOX2 from ubiquitin-dependent protein degradation. We identified UBR5 as a major ubiquitin E3 ligase that induces SOX2 degradation through ubiquitinating SOX2 at lysine 115. Phosphorylation of SOX2 at threonine 116 by AKT inhibits the interaction of UBR5 with SOX2 and thus stabilizes SOX2. We provided evidence that AKT inhibitor can effectively downregulate SOX2 and suppress esopheageal cancer cell proliferation and stemness. Taken together, our study provides new insight into the mechanism of SOX2 overexpression in cancer and evidence for targeting AKT as a potential therapeutic strategy for SOX2-positive cancers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.