Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma.
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.
Muders
Michael H
MH
Department of Biochemistry and Molecular Biology, Mayo Clinic Cancer Center, Rochester, Minnesota 55905, USA.
Dutta
Shamit K
SK
Wang
Ling
L
Lau
Julie S
JS
Bhattacharya
Resham
R
Smyrk
Thomas C
TC
Chari
Suresh T
ST
Datta
Kaustubh
K
Mukhopadhyay
Debabrata
D
D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003593:Cytoplasm / Q000737:chemistry; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000235:genetics; D046888:Tissue Array Analysis
D048868:Adaptor Proteins, Signal Transducing; C492009:GIPC1 protein, human; D012333:RNA, Messenger; D017526:Receptor, IGF Type 1