title: The Cdc14B phosphatase displays oncogenic activity mediated by the Ras-Mek signaling pathway.
abstract: Cdc14 is a dual-specific phosphatase with relevant functions during mitotic exit in yeast. The relevance of vertebrate Cdc14 phosphatases is not well understood due to the presence of two paralogs, Cdc14A and Cdc14B, and their dispensability for cell cycle progression. Here, we report that overexpression of mammalian Cdc14B, but not Cdc14A, leads to dramatic changes in morphology and malignant transformation of normal murine fibroblasts. Cdc14B disrupts the cytoskeletal F-actin organization with loss of actin stress fibers and vinculin adhesions in a phosphatase-dependent manner. These morphological changes are associated to cellular transformation, as Cdc14B-overexpressing cells display anchorage-independent growth and are able to form tumors in vivo. These alterations are similar to those induced by Ras oncogenes ,and both Cdc14B and H-RasV12 lead to similar changes in the transcriptional profile of transformed cells. Pharmacologic inhibition of the Ras-Mek pathway rescues these defects. These data suggest that Cdc14B, but not Cdc14A, is one of the few phosphatases that display oncogenic activity in mammals and point to the Ras-MAP kinase pathway as a major effector pathway during oncogenic transformation by Cdc14B.
authors.affiliation: Spanish National Cancer Research Center, Madrid, Spain.
authors.forename: Massimo
authors.initials: M
authors.lastname: Chiesa
authors.forename: María
authors.initials: M
authors.lastname: Guillamot
authors.forename: María José
authors.initials: MJ
authors.lastname: Bueno
authors.forename: Marcos
authors.initials: M
authors.lastname: Malumbres
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D020935:MAP Kinase Signaling System; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016596:Vinculin / Q000378:metabolism; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000199:Actins; D016596:Vinculin; D020929:Mitogen-Activated Protein Kinase Kinases; C541950:CDC14B protein, mouse; D054637:Dual-Specificity Phosphatases; D018631:ras Proteins