March 18, 2016 (The 717th lecture for Nanqiang Platform)-The role of Hippo signaling in liver progenitor/stem cell and cancer stem cell
Title: The role of Hippo signaling in liver progenitor/stem cell and cancer stem cell
Lecturer: Dae-Sik Lim, Ph.D.
National Creative Research Initiatives Center,
Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST),
Time: AM 10:30, March 18, 2016 (Friday).
Venue: Lecture hall E307, School of Life Sciences.
Invitor: Prof. Dawang Zhou
Lecture Abstract: The Hippo signaling pathway has emerged as a mediator of tumor suppression that is evolutionarily conserved from flies to humans. The core complex of the Hippo pathway consists of the protein kinase Hippo (MST1 and MST2 in mammals), Salvador (SAV1 or WW45), Mats (MOB1), the protein kinase Warts (LATS1 and LATS2) and transcription activator Yorkie (YAP and TAZ). Mice with genetic disruption of the Hippo pathway show two key features: expansion of tissue-specific stem /progenitor cell populations, and a hyper-regenerative response and increased cancer incidence after tissue damage. Thus, Hippo pathway restricts stem/progenitor cell proliferation during epithelial development by inhibiting YAP/TAZ activity. Of interest, Hippo pathway mutant mice showed mechanistically and histologically distinct phenotypes in the liver. Liver specific Nf2-null mice developed mixed-type tumors with both HCC and CC characteristics. Liver specific Sav1-null mice also developed either mixed- type HCC-CC or HCC with less expansion of progenitor cells, whereas deletion of Mst1 and Mst2 generated mainly HCC with more expansion of progenitor cells. We will discuss the possible distinct roles of the mammalian Hippo components in different cell types of liver and different types of liver cancers. Additionally, we will discuss how YAP activity is regulated and what downstream targets of YAP endow cancer stem cell properties and their oncogenic activity.