Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene (Cancer Cell, 2009, 16:425-438)

報告日期: 2010/04/30
報告時間: 15:10/16:00
報告學生: 許太乙
講評老師: 賴明德
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990430-3.pdf

Mst1 and Mst2 Maintain Hepatocyte Quiescence and Suppress Hepatocellular Carcinoma Development through Inactivation of the Yap1 Oncogene

Dawang Zhou, Claudius Conrad, Fan Xia, Ji-Sun Park, Bernhard Payer, Yi Yin, Gregory Y. Lauwers, Wolfgang Thasler, Jeannie T. Lee, Joseph Avruch, and Nabeel Bardeesy

Cancer Cell 16, 425–438, November 3, 2009

 

Speaker: 許太乙

Committer: 賴明德 Ph.D

 

Abstract:

In 1995, the first hippo pathway component was found in drosophila. After this finding, the hippo pathway homologs in mammalian also were discovered. The hippo pathway can regulate the organ size in drosophila. Inasmuch as Mst plays a key role which can phosphorylate all three other components in mammalian hippo pathway. The other component Yap1 is amplified in human tumor types and Yap1 overexpressed mice’s liver size overgrowth with hepatocellular carcinoma (HCC) formation. so that the authors wanted to investigate the function of Mst in hippo pathway. The authors demonstrated the Mst1/2 double knock out mice were embryonic lethality. Mst1-/-Mst2F/- mice (conditional knock out allele) with Adenovirus expressing Cre recombinase (Adeno-Cre) indeed had the hepatocyte proliferation and resistant to Fas induced apoptosis. In Mst1/2 null mice was found Yap1 and Mob1 phosphorylation decreased or absent. Mst1 reexpressed in HCC-derived cells showed that Yap1 phosphorylation increased through the Lats1/2. the HCC clinical specimen showed the low degree Yap1 phosphorylation and exhibited loss of activated Mst1. actually the Fas ligand can through Mst1/2 to activate the apoptosis cascade is still unknown the up stream and mechanism. The different kind of tissue can express the activated Mst fragment also unknown. But this data indicated the endogenous Mst1/2 play an important role in apoptosis regulation even in tumor formation.

 

Reference:

1. The Hippo–YAP pathway: new connections between regulation of

organ size and cancer. Bin Zhao, et al. Current Opinion in Cell Biology 2008, 20:638–646

2. Biosignaling of mammalian Ste20-related kinases Pin Ling, et al. Cellular Signalling 20 (2008) 12371247