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
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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
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Substituted 2-hydroxy-N-(arylalkyl)benzamide sensitizes cancer cells to metabolic stress by disrupting actin cytoskeleton and inhibiting autophagic flux.
TL;DR: It is shown that 6k disrupts the dynamics of actin cytoskeleton in human melanoma cells, affecting processes essential for the maintenance and expansion of tumours such as cell adhesion, motility, proliferation, vesicular transport, and autophagic flux.
Dissertation
Impact on angiogenesis and ER stress and its effect on chemoresistance through PlGF inhibition in a mouse model of hepatocellular carcinoma
TL;DR: The paradoxical role of the UPR is elucidated, which protects tumour cells by facilitating their adaptation to stressful conditions within the tumour microenvironment and initiates apoptosis, in order to elucidate the pathophysiology of cancer and apoptosis.
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XBP1s acts as a transcription factor of IRE1α and promotes proliferation of colon cancer cells.
TL;DR: Zhang et al. as discussed by the authors revealed a previously unknown mechanism of IRE1α expression by XBP1s and highlighted the role of this regulation in proliferation of colon cancer cells.
Dissertation
Extractos de Agaricus bisporus como moduladores de la replicación del virus de la Hepatitis C y de la progresión de la fibrosis hepática, inflamación y estrés oxidativo. Papel del complejo NLRP3 inflamasoma en la enfermedad hepática
TL;DR: The evaluation of circulating miRNA profiles represents a promising approach to assess and non-invasively monitor liver disease severity and the status of research into relevant genetic and epigenetic modifiers of NAFLD progression will be discussed.
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