A novel function for Cyclin A2: control of cell invasion via RhoA signaling.
Cyclin A2 plays a key role in cell cycle regulation. It is essential in embryonic cells and in the hematopoietic lineage yet dispensable in fibroblasts. In this paper, we demonstrate that Cyclin A2-depleted cells display a cortical distribution of actin filaments and increased migration. These defects are rescued by restoration of wild-type Cyclin A2, which directly interacts with RhoA, or by a Cyclin A2 mutant unable to associate with Cdk. In vitro, Cyclin A2 potentiates the exchange activity of a RhoA-specific guanine nucleotide exchange factor. Consistent with this, Cyclin A2 depletion enhances migration of fibroblasts and invasiveness of transformed cells via down-regulation of RhoA activity. Moreover, Cyclin A2 expression is lower in metastases relative to primary colon adenocarcinoma in matched human tumors. All together, these data show that Cyclin A2 negatively controls cell motility by promoting RhoA activation, thus demonstrating a novel Cyclin A2 function in cytoskeletal rearrangements and cell migration.
Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique, 34293 Montpellier, France.
Nikola
N
Arsic
Nawal
N
Bendris
Marion
M
Peter
Christina
C
Begon-Pescia
Cosette
C
Rebouissou
Gilles
G
Gadéa
Nathalie
N
Bouquier
Frédéric
F
Bibeau
Bénédicte
B
Lemmers
Jean Marie
JM
Blanchard
D008841:Actin Cytoskeleton / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D056751:Cyclin A2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D056751:Cyclin A2; D020742:rhoA GTP-Binding Protein