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RGS-GAIP-interacting protein controls breast cancer progression.

Publication ,  Journal Article
Wang, L; Lau, JS; Patra, CR; Cao, Y; Bhattacharya, S; Dutta, S; Nandy, D; Wang, E; Rupasinghe, CN; Vohra, P; Spaller, MR; Mukhopadhyay, D
Published in: Molecular cancer research : MCR
December 2010

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.

Duke Scholars

Published In

Molecular cancer research : MCR

DOI

EISSN

1557-3125

ISSN

1541-7786

Publication Date

December 2010

Volume

8

Issue

12

Start / End Page

1591 / 1600

Related Subject Headings

  • cdc42 GTP-Binding Protein
  • Tumor Suppressor Protein p53
  • Transplantation, Heterologous
  • Receptors, Somatomedin
  • Proto-Oncogene Proteins c-mdm2
  • PDZ Domains
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wang, L., Lau, J. S., Patra, C. R., Cao, Y., Bhattacharya, S., Dutta, S., … Mukhopadhyay, D. (2010). RGS-GAIP-interacting protein controls breast cancer progression. Molecular Cancer Research : MCR, 8(12), 1591–1600. https://doi.org/10.1158/1541-7786.mcr-10-0209
Wang, Ling, Julie S. Lau, Chitta Ranjan Patra, Ying Cao, Santanu Bhattacharya, Shamit Dutta, Debashis Nandy, et al. “RGS-GAIP-interacting protein controls breast cancer progression.Molecular Cancer Research : MCR 8, no. 12 (December 2010): 1591–1600. https://doi.org/10.1158/1541-7786.mcr-10-0209.
Wang L, Lau JS, Patra CR, Cao Y, Bhattacharya S, Dutta S, et al. RGS-GAIP-interacting protein controls breast cancer progression. Molecular cancer research : MCR. 2010 Dec;8(12):1591–600.
Wang, Ling, et al. “RGS-GAIP-interacting protein controls breast cancer progression.Molecular Cancer Research : MCR, vol. 8, no. 12, Dec. 2010, pp. 1591–600. Epmc, doi:10.1158/1541-7786.mcr-10-0209.
Wang L, Lau JS, Patra CR, Cao Y, Bhattacharya S, Dutta S, Nandy D, Wang E, Rupasinghe CN, Vohra P, Spaller MR, Mukhopadhyay D. RGS-GAIP-interacting protein controls breast cancer progression. Molecular cancer research : MCR. 2010 Dec;8(12):1591–1600.

Published In

Molecular cancer research : MCR

DOI

EISSN

1557-3125

ISSN

1541-7786

Publication Date

December 2010

Volume

8

Issue

12

Start / End Page

1591 / 1600

Related Subject Headings

  • cdc42 GTP-Binding Protein
  • Tumor Suppressor Protein p53
  • Transplantation, Heterologous
  • Receptors, Somatomedin
  • Proto-Oncogene Proteins c-mdm2
  • PDZ Domains
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice