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Automated Imaging and Analysis for the Quantification of Fluorescently Labeled Macropinosomes
Published on: August 24, 2021
Autophagic activity dictates the cellular response to oncogenic RAS
Yihua Wang1, Xiao Dan Wang, Eleonora Lapi
1Ludwig Institute for Cancer Research Ltd., Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, United Kingdom.
Summary
Autophagic activity determines cancer cell response to RAS mutations. Apoptosis-stimulating of p53 protein 2 (ASPP2) inhibits autophagy, dictating whether cells proliferate or senesce in response to oncogenic RAS.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Biology
Background:
- RAS mutations are common in human cancers, influencing both autophagy and tumorigenesis.
- Understanding cellular responses to RAS is crucial for cancer research.
- Autophagy's role in cancer progression and response to oncogenic signaling requires further elucidation.
Purpose of the Study:
- To investigate how autophagic activity influences cellular responses to oncogenic RAS.
- To identify key regulators mediating RAS-induced senescence and autophagy.
- To elucidate the mechanism by which ASPP2 affects RAS-driven cellular fate.
Main Methods:
- Utilized mouse embryonic fibroblasts expressing oncogenic RAS and varying levels of ASPP2 and autophagy-related genes (ATG5, ATG3, ATG16).
- Assessed cellular senescence and autophagic activity through molecular assays.
- Investigated protein-protein interactions between ASPP2, ATG5, ATG12, and ATG16.
Main Results:
- Autophagic activity dictates the cellular response to oncogenic RAS.
- N-terminal Apoptosis-stimulating of p53 protein 2 (ASPP2) inhibits autophagy and promotes RAS-induced senescence.
- ASPP2 inhibits RAS-induced autophagy by preventing the formation of the ATG16/ATG5/ATG12 complex.
Conclusions:
- ASPP2 acts as a key modulator of oncogenic RAS-induced autophagy.
- Modulation of autophagic activity by ASPP2 determines whether cells proliferate or undergo senescence.
- Targeting the ASPP2-autophagy axis may offer therapeutic strategies for RAS-mutated cancers.
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