YAP promotes sorafenib resistance in hepatocellular carcinoma by upregulating survivin

Ting Sun1, Wenhao Mao2, Hui Peng2

  • 1Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. sunting@zzu.edu.cn.

Abstract

Insights

Yes-associated protein (YAP) promotes sorafenib resistance in hepatocellular carcinoma (HCC) by upregulating survivin. Targeting YAP with verteporfin enhances sorafenib

Area of Science:

  • Oncology
  • Molecular Biology
  • Hepatology

Background:

  • Sorafenib is a first-line treatment for advanced hepatocellular carcinoma (HCC).
  • Secondary drug resistance limits sorafenib efficacy in HCC.
  • The role of Yes-associated protein (YAP) in sorafenib resistance is not fully understood.

Purpose of the Study:

  • To investigate the mechanism of sorafenib resistance in HCC.
  • To explore the role of YAP in mediating sorafenib resistance.
  • To evaluate YAP inhibition as a therapeutic strategy for HCC.

Main Methods:

  • Western blotting, flow cytometry, and CCK-8 assays were used.
  • Quantitative reverse transcription polymerase chain reaction (qRT-PCR) identified survivin as a YAP effector.
  • In vivo xenograft models assessed combined sorafenib and verteporfin treatment.

Main Results:

  • Sorafenib treatment increased YAP nuclear accumulation and activation, leading to apoptosis inhibition and resistance.
  • YAP promotes sorafenib resistance by upregulating survivin expression.
  • Verteporfin, a YAP inhibitor, sensitized HCC cells to sorafenib and suppressed tumor growth in vivo.

Conclusions:

  • YAP drives sorafenib resistance in HCC via survivin upregulation.
  • Targeting YAP represents a potential therapeutic strategy to overcome sorafenib resistance in HCC.

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