ArticleScientific reports2016
Inactivation of hypoxia-induced YAP by statins overcomes hypoxic resistance tosorafenib in hepatocellular carcinoma cells.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Overexpression of Yes-associated protein and its association with clinicopathological features of hepatocellular carcinoma: A meta-analysis.Liver international : official journal of the International Association for the Study of the Liver · 2017Pooled it
- Repurposing statins for choriocarcinoma: targeting the mevalonate pathway to disrupt mechanosignaling and overcome therapeutic resistance.Clinical & experimental metastasis · 2026Review
- Combining Statins with Radiotherapy for Prostate Cancer: From Photon Experience to Proton Potential.Journal of clinical medicine · 2026Review
- USP24 promotes hepatocellular carcinoma progression by deubiquitinating and stabilizing YAP1.Cancer cell international · 2025Article
- It's all downstream from here: RTK/Raf/MEK/ERK pathway resistance mechanisms in glioblastoma.Journal of neuro-oncology · 2025Review
- Nanocomposites to Overcoming Sorafenib Resistance in Hepatocellular Carcinoma Therapy.International journal of nanomedicine · 2025Review
- Emerging trends and knowledge networks in pan-cancer sorafenib resistance: a 20-year bibliometric investigation.Frontiers in pharmacology · 2025Article
- Hypoxia-Inducible Factor-Dependent and Independent Mechanisms Underlying Chemoresistance of Hypoxic Cancer Cells.Cancers · 2024Review
- Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy.Frontiers in immunology · 2024Review
- Review
- Hippo signalling in the liver: role in development, regeneration and disease.Nature reviews. Gastroenterology & hepatology · 2022Review
- CT-707 overcomes hypoxia-mediated sorafenib resistance in Hepatocellular carcinoma by inhibiting YAP signaling.BMC cancer · 2022Article
- Antitumor Effects and Mechanisms of Metabolic Syndrome Medications on Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2022Review
- Establishment and validation of a cholesterol metabolism-related prognostic signature for hepatocellular carcinoma.Computational and structural biotechnology journal · 2022Article
- YAP/Hippo Pathway and Cancer Immunity: It Takes Two to Tango.Biomedicines · 2021Review
- UDP-glucose pyrophosphorylase 2, a regulator of glycogen synthesis and glycosylation, is critical for pancreatic cancer growth.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Transcatheter arterial chemoembolization combined with Hippo/YAP inhibition significantly improve the survival of rats with transplanted hepatocellular carcinoma.Lipids in health and disease · 2021Article
- Review
- YAP promotes sorafenib resistance in hepatocellular carcinoma by upregulating survivin.Cellular oncology (Dordrecht, Netherlands) · 2021Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib is a multikinase inhibitor used as a first-line treatment for advanced hepatocellular carcinoma (HCC), but it has shown modest to low response rates. The characteristic tumour hypoxia of advanced HCC maybe a major factor underlying hypoxia-mediated treatment failure. Thus, it is urgent to elucidate the mechanisms of hypoxia-mediated sorafenib resistance in HCC. In this study, we found that hypoxia induced the nuclear translocation of Yes associate-Protein (YAP) and the subsequent transactivation of target genes that promote cell survival and escape apoptosis, thereby leading to sorafenib resistance. Statins, the inhibitors of hydroxymethylglutaryl-CoA reductase, could ameliorate hypoxia-induced nuclear translocation of YAP and suppress mRNA levels of YAP target genes both in vivo and in vitro. Combined treatment of statins with sorafenib greatly rescued the loss of anti-proliferative effects of sorafenib under hypoxia and improved the inhibitory effects on HepG2 xenograft tumour growth, accompanied by enhanced apoptosis as evidenced by the increased sub-G1 population and PARP cleavage. The expression levels of YAP and its target genes were highly correlated with poor prognosis and predicted a high risk of HCC patients. These findings collectively suggest that statins utilization maybe a promising new strategy to counteract hypoxia-mediated resistance to sorafenib in HCC patients.
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Registered trials
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