RGS-GAIP-interacting protein controls breast cancer progression.

Publication Type:

Journal Article

Source:

Molecular cancer research : MCR, Volume 8, Issue 12, p.1591-600 (2010)

Keywords:

Adaptor Proteins, Signal Transducingdigestive disease, digestive deseases Animalsdigestive disease, digestive deseases Breast Neoplasmsdigestive disease, digestive deseases cdc42 GTP-Binding Proteindigestive disease, digestive deseases Cell Growth Processesdigestive disease, digestive deseases Cell Line, Tumordigestive disease, digestive deseases Cell Movementdigestive disease, digestive deseases Disease Models, Animaldigestive disease, digestive deseases Disease Progressiondigestive disease, digestive deseases Femaledigestive disease, digestive deseases Humansdigestive disease, digestive deseases Matrix Metalloproteinase 9digestive disease, digestive deseases Micedigestive disease, digestive deseases Mice, Nudedigestive disease, digestive deseases Neoplasm Transplantationdigestive disease, digestive deseases PDZ Domainsdigestive disease, digestive deseases Proto-Oncogene Proteins c-mdm2digestive disease, digestive deseases Receptors, Somatomedindigestive disease, digestive deseases Transplantation, Heterologousdigestive disease, digestive deseases Tumor Suppressor Protein p53

Abstract:

Although the importance of RGS-GAIP-interacting protein (GIPC) in the biology of malignant cells is well known, the molecular mechanism of GIPC in the inhibition of tumor progression has not been identified. This study focused on elucidating the molecular role of GIPC in breast cancer progression. By using a human breast tumor specimen, an in vivo mouse model, and breast cancer cell lines, we showed for the first time that GIPC is involved in breast cancer progression through regulation of breast cancer cell proliferation, survival, and invasion. Furthermore, we found that the Akt/Mdm2/p53 axis, insulin-like growth factor-1 receptor, matrix metalloproteinase-9, and Cdc42 were downstream of GIPC signaling in breast cancer cells. Moreover, we showed that wild-type p53 reduced GIPC-induced breast cancer cell survival, whereas mutant p53 inhibited GIPC-induced cell invasion. Finally, we demonstrated that an N-myristoylated GIPC peptide (CR1023, N-myristoyl-PSQSSSEA) capable of blocking the PDZ domain of GIPC successfully inhibited MDA-MB-231 cell proliferation, survival, and further in vivo tumor growth. Taken together, these findings demonstrate the importance of GIPC in breast tumor progression, which has a potentially significant impact on the development of therapies against many common cancers expressing GIPC, including breast and renal cancer.