PKA-regulated VASP phosphorylation promotes extrusion of transformed cells from the epithelium.
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Date
2014-08-15ICR Author
Author
Anton, KA
Sinclair, J
Ohoka, A
Kajita, M
Ishikawa, S
Benz, PM
Renne, T
Balda, M
Jorgensen, C
Matter, K
Fujita, Y
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Epithelium
Cell Line, Transformed
Epithelial Cells
Humans
Cell Transformation, Neoplastic
Microfilament Proteins
Cyclic AMP-Dependent Protein Kinases
Cell Adhesion Molecules
Phosphoproteins
Phosphorylation
Proto-Oncogene Proteins p21(ras)
Research team
Cell Communication
Language
eng
License start date
2014-08
Citation
Journal of cell science, 2014, 127 (Pt 16), pp. 3425 - 3433
Publisher
COMPANY OF BIOLOGISTS LTD