RGS-GAIP-interacting protein controls breast cancer progression. Mol Cancer Res 2010 Dec;8(12):1591-600
Date
11/05/2010Pubmed ID
21047775Pubmed Central ID
PMC3850212DOI
10.1158/1541-7786.MCR-10-0209Scopus ID
2-s2.0-78650495520 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
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.
Author List
Wang L, Lau JS, Patra CR, Cao Y, Bhattacharya S, Dutta S, Nandy D, Wang E, Rupasinghe CN, Vohra P, Spaller MR, Mukhopadhyay DMESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAnimals
Breast Neoplasms
Cell Growth Processes
Cell Line, Tumor
Cell Movement
Disease Models, Animal
Disease Progression
Female
Humans
Matrix Metalloproteinase 9
Mice
Mice, Nude
Neoplasm Transplantation
PDZ Domains
Proto-Oncogene Proteins c-mdm2
Receptors, Somatomedin
Transplantation, Heterologous
Tumor Suppressor Protein p53
cdc42 GTP-Binding Protein
