The FEZ1/LZTS1 (LZTS1) protein is frequently downregulated in human cancers of different histo-types. 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.
Fez1/Lzts1 absence impairs Cdk1/Cdc25C interaction during mitosis and predisposes mice to cancer development / Vecchione, Andrea; 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. - In: CANCER CELL. - ISSN 1535-6108. - 11:3(2007), pp. 275-289. [10.1016/j.ccr.2007.01.014]
Fez1/Lzts1 absence impairs Cdk1/Cdc25C interaction during mitosis and predisposes mice to cancer development
VECCHIONE, ANDREA;
2007
Abstract
The FEZ1/LZTS1 (LZTS1) protein is frequently downregulated in human cancers of different histo-types. 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
