Title:Targeting AMPK Signaling Pathway to Overcome Drug Resistance for Cancer Therapy
Volume: 17
Issue: 8
Author(s): Zhiyu Wang, Pengxi Liu, Qianjun Chen, Shigui Deng, Xiaoyan Liu, Honglin Situ, Shaowen Zhong, Swei Hann, Yi Lin
Affiliation:
关键词:
AMPK，自噬，肿瘤耐药，肿瘤干细胞，代谢。
摘要: Mulitdrug resistance (MDR) is one of critical factorslimiting the efficacy of cancer chemoor
radiotherapy. Emerging evidence has indicated that MDR is a complex process regulated by multiple
factors, among which stress response molecules are considered as central players. AMP-activated
protein kinase (AMPK) is a major regulator balancing energy supply and ultimately protects cells from
harmful stresses via coordinating multiple metabolic pathways Notably, AMPK activation was recently
shown to mediate the metabolism reprogramming in drug resistant cancer cells including promoting
Warburg effects and mitochondrial biogenesis. Furthermore, AMPK activity has also been
shown to regulate the self-renewal ability of cancer stem cells that are often refractory to chemotherapy. In addition,
AMPK phosphorylation was critical in mediating autophagy induction, a process demonstrated to be effective in chemosensitivity
modulation via degrading cellular components to satisfy nutrients requirement under stressful condition.
Meanwhile, drug discovery targeting AMPK has been developed to validate the pathological significance of AMPK in
cancer prevention and treatment. Although conflicting evidence focusing on the AMPK modulation for cancer treatment is
still remained, this might be attributed to differences in AMPK isotypes in specific tissues, off-targets effects, the degree
and duration of drug administration and experimental setting of stress conditions. This review will focus on AMPK mediated
resistance to cancer therapy and discuss its potential therapeutic implication and targeting drug development.
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