PKA-regulated VASP phosphorylation promotes extrusion of transformed cells from the epithelium.

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Authors

Anton, KA
Sinclair, J
Ohoka, A
Kajita, M
Ishikawa, S
Benz, PM
Renne, T
Balda, M
Jorgensen, C
Matter, K
Fujita, Y

Document Type

Journal Article

Date

2014-08-15

Date Accepted

Date Available

Abstract

At the early stages of carcinogenesis, transformation occurs in single cells within tissues. In an epithelial monolayer, such mutated cells are recognized by their normal neighbors and are often apically extruded. The apical extrusion requires cytoskeletal reorganization and changes in cell shape, but the molecular switches involved in the regulation of these processes are poorly understood. Here, using stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative mass spectrometry, we have identified proteins that are modulated in transformed cells upon their interaction with normal cells. Phosphorylation of VASP at serine 239 is specifically upregulated in Ras(V12)-transformed cells when they are surrounded by normal cells. VASP phosphorylation is required for the cell shape changes and apical extrusion of Ras-transformed cells. Furthermore, PKA is activated in Ras-transformed cells that are surrounded by normal cells, leading to VASP phosphorylation. These results indicate that the PKA-VASP pathway is a crucial regulator of tumor cell extrusion from the epithelium, and they shed light on the events occurring at the early stage of carcinogenesis.

Citation

Journal of cell science, 2014, 127 (Pt 16), pp. 3425 - 3433

Source Title

Publisher

COMPANY OF BIOLOGISTS LTD

ISSN

0021-9533

eISSN

1477-9137

Research Team

Cell Communication

Notes