title: The role of oxidized ATM in the regulation of oxidative stress-induced energy metabolism reprogramming of CAFs.
abstract: Cancer-associated fibroblasts (CAFs) are the predominant cell type in tumor microenvironment (TM) and featured with the distinct energy metabolism reprogramming (EMR) phenotype caused by many factors such as hypoxia and growth factors. The EMR of CAFs plays a key role in biological behaviors of cancer cells including proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Recently, accumulative evidence indicates that oxidative stress (OS) mediates the EMR of CAFs under conditions of various stimuli. However, the precise mechanism by which OS causes the EMR of CAFs is not clear. Interestingly, our previous work suggested that ataxia-telangiectasia mutated (ATM) signaling is activated independent of DNA double strand breaks (DSBs) in CAFs derived from human breast cancers compared with paired normal fibroblasts (NFs). Recent studies have shown that ATM protein kinase, as a redox sensor, is closely associated with cellular energy metabolism. Thus, it is very possible that ATM protein kinase regulates the EMR of CAFs. So, it is necessary to perform an integral study on how oxidized ATM regulates the EMR of CAFs in response to various stimuli evoking OS. This will facilitate to develop a new powerful strategy of preventing and treating cancers.
authors: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors: Shifu
authors: S
authors: Tang
authors: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors: Li
authors: L
authors: Yang
authors: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China.
authors: Xi
authors: X
authors: Tang
authors: Key Laboratory of Laboratory Medical Diagnostics, Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China. Electronic address: mliu-hncq@hotmail.com.
authors: Manran
authors: M
authors: Liu
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D004734:Energy Metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D017382:Reactive Oxygen Species; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: Cancer-associated fibroblasts; Energy metabolism reprogramming; Oxidative stress; Oxidized ATM; Tumor microenvironment