期刊
JOURNAL OF CELL SCIENCE
卷 128, 期 4, 页码 781-789出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.163113
关键词
Apical extrusion; Ras; Epithelial cell; Cav-1; EPLIN
类别
资金
- Funding Program for Next Generation World-Leading Researchers (NEXT Program)
- Takeda Science Foundation
- Uehara Memorial Foundation
- Japan Society for the Promotion of Science Research Fellowship for Young Scientists (DC2)
- Grants-in-Aid for Scientific Research [26114001, 14J02366, 14J02338, 26250026] Funding Source: KAKEN
At the initial stage of carcinogenesis, a mutation occurs in a single cell within a normal epithelial layer. We have previously shown that RasV12-transformed cells are apically extruded from the epithelium when surrounded by normal cells. However, the molecular mechanisms underlying this phenomenon remain elusive. Here, we demonstrate that Cav-1-containing microdomains and EPLIN (also known as LIMA1) are accumulated in RasV12-transformed cells that are surrounded by normal cells. We also show that knockdown of Cav-1 or EPLIN suppresses apical extrusion of RasV12-transformed cells, suggesting their positive role in the elimination of transformed cells from epithelia. EPLIN functions upstream of Cav-1 and affects its enrichment in RasV12-transformed cells that are surrounded by normal cells. Furthermore, EPLIN regulates non-cell-autonomous activation of myosin-II and protein kinase A (PKA) in RasV12-transformed cells. In addition, EPLIN substantially affects the accumulation of filamin A, a vital player in epithelial defense against cancer (EDAC), in the neighboring normal cells, and vice versa. These results indicate that EPLIN is a crucial regulator of the interaction between normal and transformed epithelial cells.
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