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Updated: Jun 17, 2026
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
MST1 interactomes profiling across cell death in esophageal squamous cell carcinoma
Li Zhang1, Mingwei Gao2, Yueguang Wu1
1Cancer Institute, Shenzhen-Peking University-the Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong, China.
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.
Insights
Mammalian Ste 20-like kinase 1 (MST1) interacts with different proteins during cell death in esophageal squamous cell carcinoma (ESCC). Understanding these interactions offers new therapeutic targets for drug-resistant ESCC.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Research
Background:
- Resistance to apoptosis is a major challenge in treating esophageal squamous cell carcinoma (ESCC).
- Investigating alternative cell death pathways is crucial for overcoming drug resistance in ESCC.
Purpose of the Study:
- To explore the role of Mammalian Ste 20-like kinase 1 (MST1) in various cell death pathways (apoptosis, autophagy, pyroptosis) in ESCC.
- To identify MST1-interacting proteins during normal proliferation and different cell death processes.
Main Methods:
- Utilized enhanced ascorbate peroxidase 2 (APEX2) proximity labeling.
- Employed immunoprecipitation-mass spectrometry (IP-MS) to identify MST1 interactomes.
- Performed proteomic profiling to analyze protein functions and localization.
Main Results:
- MST1 exhibits an expanded interactome during cell death compared to normal proliferation.
- Specific protein interactions with MST1 were identified during apoptosis (e.g., INCENP, ANLN), autophagy (e.g., CBX8, YTHDC1), and pyroptosis (e.g., LRRFIP2, FLII).
- Observed changes in interacting protein expression, such as decreased STK3 during apoptosis.
Conclusions:
- MST1 and its interactomes play significant roles in regulating diverse cell death pathways in ESCC.
- These findings provide potential mechanisms for MST1 in regulating cell death.
- Further research is needed to validate and consolidate these observations for therapeutic development.
