ArticleOncotarget2016
Nuclear translocation and activation of YAP by hypoxia contributes to the chemoresistance of SN38 in hepatocellular carcinoma cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 75 citations in OpenAlex.
- Development and In Vitro Evaluation of Atorvastatin and Rutin Co-Loaded Nanoliposomes for Enhanced Anti-Inflammatory and Cytotoxic Efficacy.International journal of molecular sciences · 2026Article
- Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.Oncology research · 2026Review
- Overcoming resistance to antibody-drug conjugates: from mechanistic insights to cutting-edge strategies.Journal of hematology & oncology · 2025Review
- The multifaceted role of YAP in the tumor microenvironment and its therapeutic implications in cancer.Experimental & molecular medicine · 2025Review
- hsa_circ_0001103 correlates with unfavorable MRI features and promotes glioma progression by modulating the miR-375/YAP1 axis.Journal of molecular histology · 2025Article
- The mechanistic insights behind the anticancer effects of statins in liver cancer.Hepatology communications · 2024Article
- Fatty acid binding protein 5 suppression attenuates obesity-induced hepatocellular carcinoma by promoting ferroptosis and intratumoral immune rewiring.Nature metabolism · 2024Article
- Role of YAP Signaling in Regulation of Programmed Cell Death and Drug Resistance in Cancer.International journal of biological sciences · 2024Review
- Hypoxia-inducible factor-2α promotes fibrosis in non-alcoholic fatty liver disease by enhancing glutamine catabolism and inhibiting yes-associated protein phosphorylation in hepatic stellate cells.Frontiers in endocrinology · 2024Article
- Hypoxia-induced YAP activation and focal adhesion turnover to promote cell migration in mesenchymal TNBC cells.Cancer medicine · 2023Article
- New insights into fibrotic signaling in hepatocellular carcinoma.Frontiers in oncology · 2023Review
- The Regulation of the Hippo Pathway by Intercellular Junction Proteins.Life (Basel, Switzerland) · 2022Review
- Atorvastatin Enhances the Efficacy of Immune Checkpoint Therapy and Suppresses the Cellular and Extracellular Vesicle PD-L1.Pharmaceutics · 2022Article
- CT-707 overcomes hypoxia-mediated sorafenib resistance in Hepatocellular carcinoma by inhibiting YAP signaling.BMC cancer · 2022Article
- A role for the NPM1/PTPN14/YAP axis in mediating hypoxia-induced chemoresistance to sorafenib in hepatocellular carcinoma.Cancer cell international · 2022Article
- Yes-associated protein promotes endothelial-to-mesenchymal transition of endothelial cells in choroidal neovascularization fibrosis.International journal of ophthalmology · 2022Article
- Targeting cancer-specific metabolic pathways for developing novel cancer therapeutics.Frontiers in immunology · 2022Review
- Regression of Hepatic Fibrosis and Evolution of Cirrhosis: A Concise Review.Advances in anatomic pathology · 2021Review
- Ligustilide counteracts carcinogenesis and hepatocellular carcinoma cell-evoked macrophage M2 polarization by regulating yes-associated protein-mediated interleukin-6 secretion.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Cell competition in intratumoral and tumor microenvironment interactions.The EMBO journal · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although hypoxia is a prominent feature contributing to the therapeutic resistance of hepatocellular carcinoma cells (HCC) against chemotherapeutic agents, including the Topoisomerase I inhibitor SN38, the underlying mechanism is not fully understood and its understanding remains a major clinical challenge. In the present study, we found that hypoxia-induced nuclear translocation and accumulation of YAP acted as a survival input to promote resistance to SN38 in HCC. The induction of YAP by hypoxia was not mediated by HIF-1α because manipulating the abundance of HIF-1α with CoCl2, exogenous expression, and RNA interference had no effect on the phosphorylation or total levels of YAP. The mevalonate-HMG-CoA reductase (HMGCR) pathway may modulate the YAP activation under hypoxia. Combined YAP inhibition using either siRNA or the HMGCR inhibitor statins together with SN38 treatment produced improved anti-cancer effects in HCC cells. The increased anti-cancer effect of the combined treatment with statins and irinotecan (the prodrug of SN-38) was further validated in a human HepG2 xenograft model of HCC in nude mice. Taken together, our findings identify YAP as a novel mediator of hypoxic-resistance to SN38. These results suggest that the administration of SN28 together with the suppression of YAP using statins is a promising strategy for enhancing the treatment response in HCC patients, particularly in advanced stage HCC cases presenting hypoxic resistance.
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