ArticleCellular oncology (Dordrecht, Netherlands)2021
YAP promotes sorafenib resistance in hepatocellular carcinoma by upregulating survivin.
Article in Cellular oncology (Dordrecht, Netherlands), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- NHSL3 knockout modulates sorafenib response, growth, and motility in hepatocellular carcinoma cell models.Molecular biology reports · 2026Article
- USP25 aggravates liver cancer development and impairs chemosensitivity by limiting LATS1 activation.EMBO reports · 2026Article
- Targeting C12ORF49-Mediated Ferroptosis in Hepatocellular Carcinoma.JGH open : an open access journal of gastroenterology and hepatology · 2026Review
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- The advantages and challenges of sorafenib combination therapy: Drug resistance, toxicity and future directions (Review).Oncology letters · 2025Review
- Post-translational modifications in hepatocellular carcinoma: mechanisms and therapeutic potential.Medical oncology (Northwood, London, England) · 2025Review
- TCF12 enhances angiogenesis and affects sorafenib response in liver cancer via HIF-1α interaction.Biomolecules & biomedicine · 2025Article
- TET2 orchestrates YAP signaling to potentiate targetable vulnerability in hepatocellular carcinoma.Cell death & disease · 2025Article
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistance.Nature communications · 2025Article
- Targeting the inhibitors of apoptosis proteins (IAPs) to combat drug resistance in cancers.Frontiers in pharmacology · 2025Review
- Quercetin alleviates rifampicin-induced hepatocyte injury by modulating the Hippo-YAP signaling pathway.Frontiers in medicine · 2025Article
- Targeting the Hippo/YAP1 signaling pathway in hepatocellular carcinoma: From mechanisms to therapeutic drugs (Review).International journal of oncology · 2024Review
- Review
- Interplay between YAP/TAZ and metabolic dysfunction-associated steatotic liver disease progression.Archives of pharmacal research · 2024Review
- New Opportunities in the Systemic Treatment of Hepatocellular Carcinoma-Today and Tomorrow.International journal of molecular sciences · 2024Review
- Targeting YAP1 to improve the efficacy of immune checkpoint inhibitors in liver cancer: mechanism and strategy.Frontiers in immunology · 2024Review
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- Complex roles of Hippo-YAP/TAZ signaling in hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2023Review
- Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundSorafenib is the standard first-line treatment for advanced hepatocellular carcinoma (HCC), but its use is hampered by secondary drug resistance. Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which is crucial for liver tumorigenesis. As yet, however, the mechanism underlying sorafenib resistance and the role of YAP therein is not fully understood and needs to be explored further.
methodsWestern blotting, flow cytometry and CCK-8 assays were used to assess the role of YAP in HCC sorafenib resistance. Next, qRT-PCR and Western blotting were performed to identify survivin as a YAP downstream effector, and rescue experiments were performed to confirm that YAP induces sorafenib resistance via survivin. Additionally, Western blotting, flow cytometry and in vivo xenograft models were used to evaluate the effect of verteporfin in combination with sorafenib on HCC.
resultsWe found that sorafenib enhances YAP nuclear accumulation and activation, thereby promoting sorafenib resistance through inhibiting apoptosis in HCC cells. In addition, we found that survivin acts as a downstream mediator of YAP to resist sorafenib-induced apoptosis. Pharmacological inhibition of YAP by verteporfin increased the sensitivity of HCC cells to sorafenib and reversed sorafenib resistance. Moreover, verteporfin in combination with sorafenib significantly suppressed in vivo HCC tumor growth.
conclusionsOur data indicate that YAP promotes sorafenib resistance through upregulation of survivin expression in HCC cells. Targeting YAP may be a therapeutic strategy to improve the antitumor effects of sorafenib in HCC.
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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.