EPLIN is a crucial regulator for extrusion of RasV12-transformed cells.
J Cell Sci
; 128(4): 781-9, 2015 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-25609711
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transformação Celular Neoplásica
/
Proteínas Proto-Oncogênicas p21(ras)
/
Células Epiteliais
/
Caveolina 1
/
Proteínas dos Microfilamentos
/
Neoplasias
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article