Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma

Michael H. Muders, Shamit K. Dutta, Ling Wang, Julie S. Lau, Resham Bhattacharya, Thomas C. Smyrk, Suresh T. Chari, Kaustubh Datta, Debabrata Mukhopadhyay

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37 Scopus citations

Abstract

Regulator of G-protein signaling-GAIP-interacting protein COOH terminus (GIPC) is involved in protein trafficking, endocytosis, and receptor clustering and is associated with insulin-like growth factor I receptor (IGF-IR), a receptor important for proliferation and anchorage-independent growth. Here, we described GIPC expression in different human pancreatic adenocarcinoma (PCA) cell lines and we examined the role of GIPC in the regulation of IGF-IR protein levels in PCA. Interestingly, inhibition of GIPC expression by RNA interference led to reduced IGF-IR protein levels and a subsequent decrease in proliferation of PCA cells. We also determined that the PDZ domain of GIPC is essential for the post-translational regulation and the binding of IGF-IR. The importance of GIPC in pancreatic cancer development and progression is supported by tissue microarray data of 300 pancreatic cancer specimens where GIPC is highly expressed in PCA. Taken together, our data suggest that GIPC is a central molecule for the stability of IGF-IR and could be a target for future therapy.

Original languageEnglish (US)
Pages (from-to)10264-10268
Number of pages5
JournalCancer Research
Volume66
Issue number21
DOIs
Publication statusPublished - Nov 1 2006

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Muders, M. H., Dutta, S. K., Wang, L., Lau, J. S., Bhattacharya, R., Smyrk, T. C., ... Mukhopadhyay, D. (2006). Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma. Cancer Research, 66(21), 10264-10268. https://doi.org/10.1158/0008-5472.CAN-06-2321