RGS-GAIP-interacting protein controls breast cancer progression

Ling Wang, Julie S. Lau, Chitta Ranjan Patra, Ying Cao, Santanu Bhattacharya, Shamit Dutta, Debashis Nandy, Enfeng Wang, Chamila N. Rupasinghe, Pawan Vohra, Mark R. Spaller, Debabrata Mukhopadhyay

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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 wildtype 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.

Original languageEnglish (US)
Pages (from-to)1591-1600
Number of pages10
JournalMolecular Cancer Research
Volume8
Issue number12
DOIs
StatePublished - Dec 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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