Loss of p53 promotes RhoA-ROCK-dependent cell migration and invasion in 3D matrices.
In addition to its role in controlling cell cycle progression, the tumor suppressor protein p53 can also affect other cellular functions such as cell migration. In this study, we show that p53 deficiency in mouse embryonic fibroblasts cultured in three-dimensional matrices induces a switch from an elongated spindle morphology to a markedly spherical and flexible one associated with highly dynamic membrane blebs. These rounded, motile cells exhibit amoeboid-like movement and have considerably increased invasive properties. The morphological transition requires the RhoA-ROCK (Rho-associated coil-containing protein kinase) pathway and is prevented by RhoE. A similar p53-mediated transition is observed in melanoma A375P cancer cells. Our data suggest that genetic alterations of p53 in tumors are sufficient to promote motility and invasion, thereby contributing to metastasis.
Gadea
Gilles
G
Centre de Recherche en Biochimie Macromoléculaire, Centre National de la Recherche Scientifique, Universite Mixte de Recherche 5237, Institut Federatif de Recherche 122, F-34293 Montpellier, Cedex 5, France.
de Toledo
Marion
M
Anguille
Christelle
C
Roux
Pierre
P
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D018274:Electroporation; D004622:Embryo, Mammalian; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000032:analysis / Q000378:metabolism*
D004338:Drug Combinations; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin; D011509:Proteoglycans; D016159:Tumor Suppressor Protein p53; C059485:matrigel; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein