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ROS-induced cytosolic release of PGAM5 accelerates cancer progression via MST3-YAP axis

GSE248431 Mus musculus Expression profiling by high throughput sequencing 7 samples Submitted 2024/11/05 Platform GPL24247
Summary
Aberrant mtROS release in response to mitochondrial stress are considered to be a major novel feature of neoplastic transformation. However, the molecular mechanisms by which mtROS contribute to CRC development have not been fully elucidated. In this study, we showed that upon sensing the mtROS signal, the mitochondrially localized phosphatase PGAM5 undergoes cleavage in the mitochondrial transmembrane domain, and then the Cleaved PGAM5 is released into the cytoplasm. Subsequently, Cleaved PGAM5 binds to the kinase MST3 in the cytoplasm to promote MST3 dephosphorylation, resulting in a decrease in MST3 activity. Importantly, MST3 inactivation failed to regulate YAP phosphorylation, leading to YAP translocation into the nucleus, consequently promoting CRC proliferation and metastasis. Collectively, our findings identified the PGAM5-MST3-YAP axis as an important molecular mechanism through which mtROS promotes CRC development.
Published in
ROS-induced cytosolic release of mitochondrial PGAM5 promotes colorectal cancer progression by interacting with MST3
Wang S, Wu X, Bi W et al. · Nature communications 2025 · PMID 39915446 · doi:10.1038/s41467-025-56444-2
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Also filed as BioProject PRJNA1043738 and SRA study SRP473412. Searching any of these in the dataset finder brings you back here.

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