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J Cell Sci. 2015 Feb 15;128(4):781-9. doi: 10.1242/jcs.163113. Epub 2015 Jan 20.

EPLIN is a crucial regulator for extrusion of RasV12-transformed cells.

Author information

1
Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan.
2
Department of Biology, Faculty of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
3
Genomics, Proteomics and Biomedical Functions, Department of Life and Medical Systems, Faculty of Life and Medical Sciences, Doshisha University, 1-3 Tataramiyakodani, Kyotanabe, Kyoto 610-0394, Japan.
4
Shimadzu Corporation, Life Science Research Center, 1-3 Kanda, Nishiki-cho, Chiyoda-ku, Tokyo 101-8448, Japan.
5
Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-0815, Japan yasu@igm.hokudai.ac.jp.

Abstract

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.

KEYWORDS:

Apical extrusion; Cav-1; EPLIN; Epithelial cell; Ras

PMID:
25609711
DOI:
10.1242/jcs.163113
[Indexed for MEDLINE]
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