MST1 interactomes profiling across cell death in esophageal squamous cell carcinoma  

作　　者：Li Zhang Mingwei Gao Yueguang Wu Huijuan Liu Xuehan Zhuang Yan Zhou Qiqin Song Shanshan Bi Weimin Zhang Yongping Cui 

机构地区：[1]Cancer Institute,Shenzhen-Peking University-the Hong Kong University of Science and Technology Medical Center,Shenzhen,Guangdong 518035,China [2]Department of Oncology,Peking University Shenzhen Hospital,Shenzhen,Guangdong,China [3]Institute of Cancer Research,Shenzhen Bay Laboratory,Shenzhen,Guangdong,China

出　　处：《Medical Review》2024年第6期531-543,共13页医学评论(英文)

基　　金：supported by the funds of Guangdong Basic and Applied Basic Research Foundation(2019B030302012);the National Key R&D Program of China(2021YFC2501001,2022YFC3401002);Shenzhen Medical Research Funds(C2303002);the National Natural Science Foundation of China(82341024,82172930,82203286);the Major Program of Shenzhen Bay Laboratory(S201101004);China Postdoctoral Science Foundation(BX20220214).

摘　　要：Objectives:Resistance to apoptosis in esophageal squamous cell carcinoma(ESCC)constitutes a significant impediment to treatment efficacy.Exploring alternative cell death pathways and their regulatory factors beyond apoptosis is crucial for overcoming drug resistance and enhancing therapeutic outcomes in ESCC.Methods:Mammalian Ste 20-like kinase 1(MST1)is implicated in regulating various cell deaths,including apoptosis,autophagy,and pyroptosis.Employing enhanced ascorbate peroxidase 2(APEX2)proximity labeling coupled with immunoprecipitation-mass spectrometry(IP-MS),we elucidated the interactomes of MST1 across these three cell death paradigms.Results:Proteomic profiling unveiled the functional roles and subcellular localization of MST1 and its interacting proteins during normal proliferation and various cell death processes.Notably,MST1 exhibited an expanded interactome during cell death compared to normal proliferation and chromosome remodeling functions consistently.In apoptosis,there was a notable increase of mitosis-associated proteins such as INCENP,ANLN,KIF23,SHCBP1 and SUPT16H,which interacted with MST1,alongside decreased expression of the pre-apoptotic protein STK3.During autophagy,the bindings of DNA repair-related proteins CBX8 and m6A reader YTHDC1 to MST1 were enhanced.In pyroptosis,LRRFIP2 and FLII which can inhibit pyroptosis increasingly binding to MST1.Conclusions:Our findings delineate potential mechanisms through which MST1 and its interactomes regulate cell death,paving the way for further investigation to validate and consolidate these observations.

关 键 词：MST1 cell death ESCC PROTEOMICS APEX2 

分 类 号：R73[医药卫生—肿瘤]