ArticleJournal of experimental & clinical cancer research : CR2019
DEPTOR induces a partial epithelial-to-mesenchymal transition and metastasis via autocrine TGFβ1 signaling and is associated with poor prognosis in hepatocellular carcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- [PSMD11 overexpression promotes epithelial-mesenchymal transition in gastric cancer and affects patient prognosis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Constructing a chemokine-based model and identifyingTranslational cancer research · 2025Article
- TGF-β1-Induced LINC01094 promotes epithelial-mesenchymal transition in hepatocellular carcinoma through the miR-122-5p/TGFBR2-SAMD2-SMAD3 Axis.Functional & integrative genomics · 2024Article
- The UBE2C/CDH1/DEPTOR axis is an oncogene and tumor suppressor cascade in lung cancer cells.The Journal of clinical investigation · 2023Article
- Repair of Limb Ischemia Is Dependent on Hematopoietic Stem Cell Specific-SHP-1 Regulation of TGF-β1.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Heterogeneity, inherent and acquired drug resistance in patient-derived organoid models of primary liver cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Co-amplification of genes in chromosome 8q24: a robust prognostic marker in hepatocellular carcinoma.Journal of gastrointestinal oncology · 2021Article
- Regulatory role of DEPTOR‑mediated cellular autophagy and mitochondrial reactive oxygen species in angiogenesis in multiple myeloma.International journal of molecular medicine · 2021Article
- Autocrine TGF-β in Cancer: Review of the Literature and Caveats in Experimental Analysis.International journal of molecular sciences · 2021Review
- Prognostic Value of LHFPL Tetraspan Subfamily Member 6Pharmacogenomics and personalized medicine · 2021Article
- Comprehensive analysis of partial epithelial mesenchymal transition-related genes in hepatocellular carcinoma.Journal of cellular and molecular medicine · 2021Article
- Modulation of the TGF-β signaling pathway by long noncoding RNA in hepatocellular carcinoma.Biomarker research · 2020Review
- A novel prognostic models for identifying the risk of hepatocellular carcinoma based on epithelial-mesenchymal transition-associated genes.Bioengineered · 2020Article
- Emerging Concepts of Hybrid Epithelial-to-Mesenchymal Transition in Cancer Progression.Biomolecules · 2020Review
- Unresolved Complexity in the Gene Regulatory Network Underlying EMT.Frontiers in oncology · 2020Review
- Type-2 11β-hydroxysteroid dehydrogenase promotes the metastasis of colorectal cancer via the Fgfbp1-AKT pathway.American journal of cancer research · 2020Article
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundDEPTOR is an endogenous inhibitor of mTORC1 and mTORC2 that plays a vital role in the progression of human malignances. However, the biological function of DEPTOR in HCC metastasis and the underlying molecular mechanisms are still unclear.
methodsWestern blot analysis and immunohistochemistry(IHC) were employed to examine DEPTOR expression in HCC cell lines and tissues. A series of in vivo and in vitro assays were performed to determine the function of DEPTOR and the possible mechanisms underlying its role in HCC metastasis.
resultsWe found that DEPTOR was frequently overexpressed in HCC tissues, and its high expression was associated with high serum AFP levels, increased tumor size, vascular invasion and more advanced TMN and BCLC stage, as well as an overall poor prognosis. Functional experiments demonstrated that DEPTOR silencing inhibited the proliferation and mobility of HCC cells in vitro and suppressed tumor growth and metastasis of HCC cells in vivo. Accordingly, DEPTOR overexpression promoted the invasion and metastasis of HCC cells in vitro and in vivo, but had no effect on cell proliferation in vitro. Overexpression of DEPTOR induced EMT by snail induction. Conversely, knockdown of snail expression impaired the DEPTOR-induced migration, invasion and EMT of HCC cells. Furthermore, we found that the increase of snail expression by DEPTOR overexpression was due to an activation of TGF-β1-smad3/smad4 signaling possibly through feedback inhibition of mTOR.
conclusionDEPTOR promotes the EMT and metastasis of HCC cells by activating the TGF-β1-smad3/smad4-snail pathway via mTOR inhibition. Therefore, targeting DEPTOR may be an ideal treatment strategy for inhibiting the growth and metastasis of HCC.
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