WIP1 promotes cancer stem cell properties by inhibiting p38 MAPK in NSCLC
作者机构：School of MedicineNankai UniversityTianjin 30071China Departments of Immunology and Microbial ScienceThe Scripps Research InstituteLa JollaCA 92037USA Department of Cancer Biology and Wake Forest Baptist Comprehensive Cancer CenterWake Forest School of MedicineWinston-SalemNC 27157USA Department of Respiratory DiseaseSouth CampusRenji HospitalSchool of Medicine Shanghai Jiaotong UniversityShanghaiChina
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2020年第5卷第1期
页 面：2055-2064页
核心收录：
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：supported by NIH/NCI grants(CA131231,CA172115,P30CA012197 to P.S.) the National Key Research and Development Program of China(2018YFE0114300 to R.X.) the National Natural Science Foundation of China(No.81972454(S.Y.),81972882(R.X.)).P.S.is supported by the Anderson Oncology Research Professorship
摘 要：Cancer stem cells(CSCs)are a small population of stem cell-like cancer cells that can initiate tumors in vivo,and are the major source of cancer initiation,relapse,and drug *** previously reported that the p38 MAPK,through its downstream effectors MK2 and HSP27,suppressed CSC properties by downregulating the expression of transcription factors that mediate stemness in non-small-cell lung cancer(NSCLC)cells,and that despite unaltered total expression of total p38 proteins,the levels of activated p38 were reduced in NSCLC ***,the mechanism underlying the reduced levels of activated p38 in NSCLC is *** this study,we identified WIP1,a p38 phosphatase frequently overexpressed in cancer,as a suppressor of p38 in a pathway that regulates CSC properties in *** WIP1 expression correlated with reduced levels of activated p38,and with increased levels of a CSC marker in NSCLC *** investigation revealed that WIP1 promoted stemness-related protein expression and CSC properties by inhibiting p38 activity in NSCLC ***1 inhibitors are currently under development as anticancer drugs based on their ability to reactivate *** found that a WIP1 inhibitor suppressed stemness-related protein expression and CSC properties by activating p38 in NSCLC cells in vitro and in *** studies have identified the WIP1–p38–MK2–HSP27 cascade as a novel signaling pathway that,when altered,promotes CSC properties in NSCLC development,and have defined novel mechanisms underlying the oncogenic activity of WIP1 and the anticancer efficacy of WIP1 inhibitors.
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