DOI: 10.1515/mr-2024-0031
MST1 interactomes profiling across cell death in esophageal squamous cell carcinoma
Li Zhang1
Mingwei Gao2
Yueguang Wu1
Huijuan Liu3
Xuehan Zhuang1
Yan Zhou3
Qiqin Song1
Shanshan Bi1
Weimin Zhang4
Yongping Cui4
1.Cancer Institute,Shenzhen-Peking University-the Hong Kong University of Science and Technology Medical Center,Shenzhen,Guangdong,China2.Department of Oncology,Peking University Shenzhen Hospital,Shenzhen,Guangdong,China3.Institute of Cancer Research,Shenzhen Bay Laboratory,Shenzhen,Guangdong,China4.Cancer Institute,Shenzhen-Peking University-the Hong Kong University of Science and Technology Medical Center,Shenzhen,Guangdong 518035,China
摘要：Objectives:Resistance to apoptosis in esophageal squa-mous 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 impli-cated 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 eluci-dated 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 inter-actome 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.
机标关键词：profilingcellacrosscarcinomadeathesophagealinteractomessquamous
论文发表日期：2024-12-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
英文信息