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Role of Gab2 in mammary tumorigenesis and metastasis

2007; Springer Nature; Volume: 26; Issue: 34 Linguagem: Inglês

10.1038/sj.onc.1210315

1476-5594

Yuehai Ke, Di Wu, Frédéric Princen, Thùy Linh Nguyễn, Yanli Pang, Jacqueline Lesperance, William J. Muller, Robert G. Oshima, G-S Feng,

14-3-3 protein interactions

Overexpression of the adaptor/scaffolding protein Gab2 has been detected in primary human breast cancer cells and cell lines, although its functional significance in breast carcinogenesis is not fully understood. Here, we show a requirement for Gab2 in promoting mammary tumor metastasis. Although Gab2 expression levels were elevated in mammary tumors induced by the Neu (ErbB-2) oncogene, homozygous deletion of Gab2 in mice had only a modest effect on the initiation of Neu-induced mammary tumors. Notably, ablation of Gab2 severely suppressed lung metastasis. Gab2-deficient cancer cells displayed normal Akt activities, and their proliferative rate in vitro was similar to control cells. However, Gab2−/− cancer cells exhibited decreased migration and impaired Erk activation, and the defects were rescued by re-introduction of Gab2 into Gab2−/− cells. These findings suggest that although Gab2 overexpression may confer growth advantage to tumor cells, the functional requirement for Gab2 in mammary tumor initiation/growth may be dispensable, and that Gab2 may have a prominent role in promoting mammary tumor metastasis.