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Reduced expression of RhoE promotes ROCK-dependent invasion in transformed human fibroblasts

ABSTRACT: Cen3tel cells, obtained by telomerase immortalization of human fibroblasts, gradually underwent neoplastic transformation and became metastatic in immunocompromised mice. Neoplastic transformation was associated with a change in cell morphology (from fibroblastic to polygonal). Tumorigenic cells acquired a clear-cut membrane localization of adhesion molecules, a reorganization of the actin cytoskeleton, increased cell motility and invasiveness. In a 3-dimensional environment, tumorigenic cells showed a spherical morphology with cortical actin rings, suggesting a switch from a mesenchymal to an amoeboid ROCK-dependent movement. Accordingly, cell invasion decreased upon treatment with the ROCK inhibitor Y27632, but not with the matrix protease inhibitor Ro28-2653. The increased invasiveness of tumorigenic cen3tel cells was associated with a reduced expression of RhoE, a cellular inhibitor of ROCK. Ectopic RhoE expression decreased cen3tel invasion capability. These results point to RhoE and ROCK as regulators of invasiveness of mesenchymal tumor cells and indicate ROCK as a possible therapeutic target. The cen3tel telomerase immortalized cell line was obtained from primary cen3 fibroblasts, derived from a centenarian individual, by infection with an hTERT-containing retrovirus (Mondello et al., 2003). Cen3tel cells were used at different steps of propagation, reflecting different phases of transformation (Zongaro et al., 2005) to study variations in the migratory and invasive potential accompanying human fibroblast neoplastic transformation. Raw data files: *NORM.txt test is Cy5 and *DS.txt test is Cy3.

ORGANISM(S): Homo sapiens  

SUBMITTER: Maurizia Mello-Grand  Ilaria Chiodi   Elena Giulotto   Katiuscia Bonezzi   Roberta Frapolli   Angelo P Dei Tos   Chiara Mondello   Francesco Favero   Cristina Belgiovine   giovanna chiorino   Maurizio D’Incalci   Giulia Taraboletti    

PROVIDER: E-GEOD-15742 | ArrayExpress | 2014-05-03



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