Loss of RhoB expression promotes migration and invasion of human bronchial cells via activation of AKT1.
Lung cancer is the leading cause of cancer-related death worldwide, mainly due to its highly metastatic properties. Previously, we reported an inverse correlation between RhoB expression and the progression of the lung cancer, occurring between preinvasive and invasive tumors. Herein, we mimicked the loss of RhoB observed throughout lung oncogenesis with RNA interference in nontumoral bronchial cell lines and analyzed the consequences on both cell transformation and invasion. Down-regulation of RhoB did not modify the cell growth properties but did promote migration and invasiveness. Furthermore, RhoB depletion was accompanied by modifications of actin and cell adhesion. The specific activation of the Akt1 isoform and Rac1 was found to be critical for this RhoB-mediated regulation of migration. Lastly, we showed that RhoB down-regulation consecutive to K-RasV12 cell transformation is critical for cell motility but not for cell proliferation. We propose that RhoB loss during lung cancer progression relates to the acquisition of invasiveness mediated by the phosphatidylinositol 3-kinase (PI3K)/AKT and Rac1 pathways rather than to tumor initiation.
Bousquet
Emilie
E
Département Innovation Thérapeutique et Oncologie Moléculaire, Institut National de la Sante et de la Recherche Medicale U563, Université de Toulouse, UPS, Centre de Physiopathologie Toulouse Purpan, Toulouse, France.
Mazières
Julien
J
Privat
Maud
M
Rizzati
Virginie
V
Casanova
Anne
A
Ledoux
Adeline
A
Mery
Eliane
E
Couderc
Bettina
B
Favre
Gilles
G
Pradines
Anne
A
D000818:Animals; D001980:Bronchi / Q000201:enzymology* / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D015536:Down-Regulation; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D008648:Mesoderm / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020743:rhoB GTP-Binding Protein / Q000096:biosynthesis / Q000172:deficiency*
C107953:RAC1 protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D016283:Proto-Oncogene Proteins p21(ras); D020830:rac1 GTP-Binding Protein; D020743:rhoB GTP-Binding Protein