Genetic Analysis of The Hippo Pathway In Mouse Liver

<p>Cancer therapy and tumor treatment remain unsolved puzzles. Genetic screening for tumor suppressor genes in <em>Drosophila</em> revealed the Hippo-signaling pathway as a kinase cascade consisting of five core components. Disrupting the pathway by deleting the main component genes breaks the balance of cell proliferation and apoptosis and results in epithelial tissue tumorigenesis. The pathway is therefore believed to be a tumor suppressor pathway. However, a corresponding role in mammals is yet to be determined. Our lab began to investigate the tumor suppression function of the potent mammalian Hippo pathway by putting floxed alleles into the mouse genome flanking the functional-domain-expressing exons in each component (<em>Mst1, Mst2, Sav1, Lats1</em> and <em>Lats2</em>). These mice were then crossed with different cre-mouse lines to generate conditional knockout mice. Results indicate a ubiquitous tumor suppression function of these components, predominantly in the liver. A further liver specific analysis of the deletion mutation of these components, as well as the <em>Yap/Taz</em> double deletion mutation, reveals essential roles of the Hippo pathway in regulating hepatic quiescence and embryonic liver development. One of the key cellular mechanisms for the Hippo pathway’s involvement in these liver biological events is likely its cell cycle regulation function. Our work will help to develop potential therapeutic approaches for liver cancer.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2012

Author dc:creator

• Lu, Li

Contributors dc:contributor

• Randy L. Johnson
• Richard R. Behringer
• Michelle C. Barton

• Hippo pathway
• Liver caner
• organ size control
• Mst
• Sav1
• Lats
• Yap
• Taz
• Cancer Biology
• Developmental Biology
• Genetics
• Medicine and Health Sciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/292

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1327