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SerpinB3 and Yap Interplay Increases Myc Oncogenic Activity.
Cristian Turato1, Stefania Cannito2, Davide Simonato1
1Dept. of Medicine, University of Padova, Italy.
Scientific Reports
|December 5, 2015
Summary
SerpinB3 enhances liver cancer by increasing Myc production. It directly inhibits Myc cleavage and indirectly activates the Yap pathway, promoting tumor growth.
Area of Science:
- Hepatology
- Molecular Oncology
- Carcinogenesis research
Background:
- SerpinB3 is an early marker of liver carcinogenesis.
- Myc overexpression correlates with aggressive tumors.
- Yes-associated protein (Yap) regulates proliferation and is upregulated in hepatocellular carcinomas.
Purpose of the Study:
- To investigate the interplay between SerpinB3 and Myc in liver cancer.
- To characterize the functional modulation of Myc by SerpinB3.
Main Methods:
- Utilized transgenic mice and hepatoma cells overexpressing SerpinB3.
- Investigated molecular mechanisms involving calpain and the Hippo pathway.
- Performed in vitro inhibition assays with human recombinant SerpinB3.
Main Results:
- SerpinB3 up-regulated Myc through calpain and Hippo-dependent pathways.
- SerpinB3 inhibited Calpain activity in vitro, reducing Myc cleavage.
- SerpinB3 indirectly increased Myc transcription via Yap pathway activation.
Conclusions:
- SerpinB3 promotes Myc production through direct and indirect mechanisms.
- Inhibition of Myc cleavage and Yap pathway activation are key roles of SerpinB3 in liver cancer.
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