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Sci Rep. 2017 Mar 10;7:44328. doi: 10.1038/srep44328.

Plectin is a novel regulator for apical extrusion of RasV12-transformed cells.

Author information

1
Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
2
Graduate School of Medicine, Hokkaido University, Sapporo 060-0815, Japan.
3
Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, Japan.
4
Genomics, Proteomics and Biomedical Functions, Department of Life and Medical Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe City 610-0394, Japan.
5
SHIMADZU Corporation, Tokyo 101-8448, Japan.

Abstract

Several lines of evidence have revealed that newly emerging transformed cells are often eliminated from the epithelium, though the underlying molecular mechanisms of this cancer preventive phenomenon still remain elusive. In this study, using mammalian cell culture systems we have identified plectin, a versatile cytoskeletal linker protein, as a novel regulator for apical extrusion of RasV12-transformed cells. Plectin is accumulated in RasV12 cells when they are surrounded by normal epithelial cells. Similarly, cytoskeletal proteins tubulin, keratin, and Epithelial Protein Lost In Neoplasm (EPLIN) are also accumulated in the transformed cells surrounded by normal cells. Knockdown or functional disruption of one of these molecules diminishes the accumulation of the others, indicating that the accumulation process of the individual protein mutually depends on each other. Furthermore, plectin-knockdown attenuates caveolin-1 (Cav-1) enrichment and PKA activity in RasV12 cells and profoundly suppresses the apical extrusion. These results indicate that the plectin-microtubules-EPLIN complex positively regulates apical elimination of RasV12-transformed cells from the epithelium in a coordinated fashion. Further development of this study would open a new avenue for cancer preventive medicine.

PMID:
28281696
PMCID:
PMC5345014
DOI:
10.1038/srep44328
[Indexed for MEDLINE]
Free PMC Article

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