Active Gα Mutants Accelerate Breast Tumor Metastasis via the c-Src Pathway.

Constitutively active mutations in the Gα and Gα subunits of heterotrimeric G proteins have been found in various human cancers, including breast cancer, but their precise roles in tumor formation, progression, and metastasis remain poorly understood. This study focused on GαR243H and GαR179C mutants in breast cancer. These mutants alone were insufficient to initiate mammary tumor formation in mice.

Active Gαi/o mutants accelerate breast tumor metastasis via the c-Src pathway.

Constitutively active mutations in the Gα and Gα subunits of heterotrimeric G proteins have been identified in several human cancers including breast cancer, but their functional significance in tumorigenesis and metastasis has not been well characterized. In this study, we show that expression of the constitutively active GαR243H and GαR179C mutants alone was insufficient to induce mammary tumor formation in mice. However, in transgenic mouse models of breast cancer induced by Neu expression or PTEN loss, we found that the GαR179C mutant enhanced spontaneous lung metastasis while having no effect on primary tumor initiation and growth.