(The) Hippo-Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis = Hippo-Salvador 신호전달체계의 간내 전구세포 분열 조절 및 간암발병기전에 관한 연구

Cited 0 time in webofscience Cited 0 time in scopus
  • Hit : 440
  • Download : 0
Loss of Hippo signaling in $\it{Drosophila}$ leads to tissue overgrowth as a result of increased cell proliferation and decreased cell death. YAP (a homolog of $\it{Drosophila}$ Yorkie and target of the Hippo pathway) was recently implicated in control of organ size, epithelial tissue development, and tumorigenesis in mammals. However, the role of the mammalian Hippo pathway in such regulation has remained unclear. I now show that mice with liver-specific ablation of WW45 (a homolog of $\it{Drosophila}$ Salvador and adaptor for the Hippo kinase) manifest increased liver size and expansion of hepatic progenitor cells (oval cells) and eventually develop hepatomas. Moreover, ablation of WW45 increased the abundance of YAP and induced its localization to the nucleus in oval cells, likely accounting for their increased proliferative capacity, but not in hepatocytes. Liver tumors that developed in mice heterozygous for $\it{WW45}$ deletion or with liver-specific WW45 ablation showed a mixed pathology combining characteristics of hepatocellular carcinoma and cholangiocarcinoma and appeared to originate from oval cells. Together, my results suggest that the mammalian Hippo-Salvador pathway restricts the proliferation of hepatic oval cells and thereby controls liver size and prevents the development of oval cell-derived tumors.
Advisors
Lim, Dae-Sikresearcher임대식researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2010
Identifier
455360/325007  / 020065114
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2010.08, [ vi, 99 p. ]

Keywords

WW45; hepatoma; DDC diet; conditional knockout mice; YAP; YAP; WW45; 간암; DDC 첨가사료; 조직 특이적 적중 마우스

URI
http://hdl.handle.net/10203/27709
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=455360&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
Files in This Item
There are no files associated with this item.

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0