Therapeutic strategies targeting AMPK-dependent autophagy in cancer cells |
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| Institution: | 1. Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan, China;2. Membrane Protein Disease Research Group, Department of Physiology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada;3. Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada;4. Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada;1. Cancer Research Program-12, Rajiv Gandhi Centre for Biotechnology (DBT-RGCB), Thycaud. P.O. Thiruvananthapuram-14, Kerala, India;2. Manipal Academy of Higher Education, Tiger Circle Road, Madhav Nagar, Manipal, Karnataka 576104, India;3. Neuro Stem Cell Biology Laboratory, Neurobiology Division, Rajiv Gandhi Centre for Biotechnology (DBT-RGCB), Thiruvananthapuram, Kerala 695 014, India;4. Regional Centre for Biotechnology (DBT-RCB), Faridabad, Haryana 121001, India;1. College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea;2. Department of Otolaryngology-Head and Neck Surgery, Center for Thyroid Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea;1. Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India;2. Center for DNA Repair and Genome Stability (CDRGS), Manipal Academy of Higher Education, Manipal, Karnataka 576104, India;3. Department of Biotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India |
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| Abstract: | Macroautophagy is a health-modifying process of engulfing misfolded or aggregated proteins or damaged organelles, coating these proteins or organelles into vesicles, fusion of vesicles with lysosomes to form autophagic lysosomes, and degradation of the encapsulated contents. It is also a self-rescue strategy in response to harsh environments and plays an essential role in cancer cells. AMP-activated protein kinase (AMPK) is the central pathway that regulates autophagy initiation and autophagosome formation by phosphorylating targets such as mTORC1 and unc-51 like activating kinase 1 (ULK1). AMPK is an evolutionarily conserved serine/threonine protein kinase that acts as an energy sensor in cells and regulates various metabolic processes, including those involved in cancer. The regulatory network of AMPK is complicated and can be regulated by multiple upstream factors, such as LKB1, AKT, PPAR, SIRT1, or noncoding RNAs. Currently, AMPK is being investigated as a novel target for anticancer therapies based on its role in macroautophagy regulation. Herein, we review the effects of AMPK-dependent autophagy on tumor cell survival and treatment strategies targeting AMPK. |
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