Fez1/Lzts1 absence impairs Cdk1/Cdc25C interaction during mitosis and predisposes mice to cancer development.

Abstract	The FEZ1/LZTS1 (LZTS1) protein is frequently downregulated in human cancers of different histotypes. LZTS1 is expressed in normal tissues, and its introduction in cancer cells inhibits cell growth and suppresses tumorigenicity, owing to an accumulation of cells in G2/M. Here, we define its role in cell cycle regulation and tumor progression by generating Lzts1 knockout mice. In Lzts1(-/-) mouse embryo fibroblasts (MEFs), Cdc25C degradation was increased during M phase, resulting in decreased Cdk1 activity. As a consequence, Lzts1(-/-) MEFs showed accelerated mitotic progression, resistance to taxol- and nocodazole-induced M phase arrest, and improper chromosome segregation. Accordingly, Lzts1 deficiency was associated with an increased incidence of both spontaneous and carcinogen-induced cancers in mice.
Authors	Andrea Vecchione, Gustavo Baldassarre, Hideshi Ishii, Milena S Nicoloso, Barbara Belletti, Fabio Petrocca, Nicola Zanesi, Louise Y Y Fong, Sabrina Battista, Daniela Guarnieri, Raffaele Baffa, Hansjuerg Alder, John L Farber, Peter J Donovan, Carlo M Croce
Journal	Cancer cell (Cancer Cell) Vol. 11 Issue 3 Pg. 275-89 (Mar 2007) ISSN: 1535-6108 [Print] United States
PMID	17349584 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents Carcinogens Cell Cycle Proteins Tumor Suppressor Proteins nitrosobenzylmethylamine CDC2 Protein Kinase CDC25C protein, human Cdc25c protein, mouse cdc25 Phosphatases Dimethylnitrosamine Paclitaxel Nocodazole
Topics	Animals Antineoplastic Agents (pharmacology) CDC2 Protein Kinase (physiology) Carcinogens Cell Cycle Proteins (physiology) Cell Division Cell Transformation, Neoplastic Cells, Cultured Chromosome Segregation Dimethylnitrosamine (analogs & derivatives) Fibroblasts (metabolism, pathology) Mice Mice, Knockout Mitosis Molecular Sequence Data Nocodazole (pharmacology) Paclitaxel (pharmacology) Stomach Neoplasms (chemically induced, genetics, pathology) Tumor Suppressor Proteins (genetics, physiology) cdc25 Phosphatases (physiology)

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