Targeting autophagy enhances sorafenib lethality for hepatocellular carcinoma via ER stress-related apoptosis.
Ying Hong Shi,Zhen-Bin Ding,Jian Zhou,Bo Hui,Guo-Ming Shi,Ai-Wu Ke,Xiaoying Wang,Zhi Dai,Yuan Fei Peng,Cheng Yu Gu,Shuang Jian Qiu,Jia Fan +11 more
Reads0
Chats0
TLDR
Findings indicated that both ER stress and autophagy were involved in the cell death evoked by sorafenib in HCC cells, indicating that the combination of Autophagy modulation and molecular targeted therapy is a promising therapeutic strategy in treatment of HCC.Abstract:
Sorafenib, a potent multikinase inhibitor, has been recognized as the standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC). However, the direct functional mechanism of tumor lethality mediated by sorafenib remains to be fully characterized, and the precise mechanisms of drug resistance are largely unknown. Here, we showed sorafenib induced both apoptosis and autophagy in human HCC cells through a mechanism that involved endoplasmic reticulum (ER) stress and was independent of the MEK1/2-ERK1/2 pathway. Upregulation of IRE1 signals from sorafenib-induced ER stress was critical for the induction of autophagy. Moreover, autophagy activation alleviated the ER stress-induced cell death. Inhibition of autophagy using either pharmacological inhibitors or essential autophagy gene knockdown enhanced cell death in sorafenib treated HCC cell lines. Critically, the combination of sorafenib with the autophagy inhibitor chloroquine produced more pronounced tumor suppression in HCC both ...read more
Citations
More filters
Journal ArticleDOI
Deconvoluting the context-dependent role for autophagy in cancer
TL;DR: In this article, the authors define the context-specific role for autophagy in cancer and the mechanisms involved will be important to guide autoophagy-based therapeutic intervention, which can be either tumour suppressive or tumour promoting.
Journal ArticleDOI
Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment
Xinbing Sui,R Chen,Z Wang,Z Huang,Na Kong,M Zhang,Weidong Han,Fang Lou,Jing Yang,Qian Zhang,Xian Wang,Chao He,Hongming Pan +12 more
TL;DR: Understanding the novel function of autophagy may allow us to develop a promising therapeutic strategy to enhance the effects of chemotherapy and improve clinical outcomes in the treatment of cancer patients.
Journal ArticleDOI
Role of the Microenvironment in the Pathogenesis and Treatment of Hepatocellular Carcinoma
Virginia Hernandez–Gea,Virginia Hernandez–Gea,Sara Toffanin,Scott L. Friedman,Josep M. Llovet +4 more
TL;DR: Increasing the understanding of how stromal components interact with cancer cells and the signaling pathways involved could help identify new therapeutic and chemopreventive targets.
Journal ArticleDOI
Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer
TL;DR: The tumorigenic and immunoregulatory effects of ER stress in cancer are discussed, and the concept of targeting ER stress responses to enhance the efficacy of standard chemotherapies and evolving cancer immunotherAPies in the clinic is explored.
Journal ArticleDOI
Autophagy and Cancer Therapy
Paola Maycotte,Andrew Thorburn +1 more
TL;DR: Recent research related to autophagy and cancer therapy is discussed with a focus on how these processes may be manipulated to improve cancer therapy.
References
More filters
Journal ArticleDOI
Molecular Targeted Therapy of Hepatocellular Carcinoma
TL;DR: This review will focus on what is currently known about the molecular pathogenesis of HCC, and explore the currently available and future molecular based therapies targeting these pathways.
Related Papers (5)
Sorafenib in Advanced Hepatocellular Carcinoma
Josep M. Llovet,Sergio Ricci,Vincenzo Mazzaferro,Philip Hilgard,Edward Gane,Jean-Frédéric Blanc,André Cosme de Oliveira,Armando Santoro,Jean-Luc Raoul,Alejandro Forner,Myron Schwartz,Camillo Porta,Stefan Zeuzem,Luigi Bolondi,Tim F. Greten,Peter R. Galle,Jean Francois Seitz,Ivan Borbath,Dieter Häussinger,Tom Giannaris,Minghua Shan,M. Moscovici,D. Voliotis,Jordi Bruix +23 more
Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial.
Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis
Kurt Degenhardt,Robin Mathew,Robin Mathew,Brian Beaudoin,Brian Beaudoin,Kevin Bray,Diana Anderson,Guanghua Chen,Guanghua Chen,Guanghua Chen,Chandreyee Mukherjee,Chandreyee Mukherjee,Chandreyee Mukherjee,Yufang Shi,Céline Gélinas,Céline Gélinas,Yongjun Fan,Deirdre A. Nelson,Shengkan Jin,Eileen White +19 more