Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma
Expression and regulatory role of GAIP-interacting protein GIPC in pancreatic adenocarcinoma
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DOI：
10.1158/0008-5472.can-06-2321
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发表时间：
2006-11-01
期刊：
影响因子：
11.2
通讯作者：
Mukhopadhyay, Debabrata
中科院分区：
文献类型：
--
作者：
Muders, Michael H.;Dutta, Shamit K.;Mukhopadhyay, Debabrata
G蛋白信号调节因子 - GAIP相互作用蛋白羧基末端（GIPC）参与蛋白质运输、内吞作用和受体聚集，并与胰岛素样生长因子I受体（IGF - IR）相关，IGF - IR是一种对增殖和非贴壁生长很重要的受体。在此，我们描述了GIPC在不同人类胰腺腺癌（PCA）细胞系中的表达，并研究了GIPC在调节PCA中IGF - IR蛋白水平方面的作用。有趣的是，通过RNA干扰抑制GIPC表达导致IGF - IR蛋白水平降低，随后PCA细胞增殖减少。我们还确定GIPC的PDZ结构域对IGF - IR的翻译后调节和结合至关重要。300例胰腺癌标本的组织芯片数据支持了GIPC在胰腺癌发生和发展中的重要性，其中GIPC在PCA中高表达。综上所述，我们的数据表明GIPC是IGF - IR稳定性的核心分子，可能成为未来治疗的靶点。
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.