Dataset Information

IGFBP2 Activates the NF-?B Pathway to Drive Epithelial-Mesenchymal Transition and Invasive Character in Pancreatic Ductal Adenocarcinoma.

ABSTRACT: The molecular basis underlying the particularly aggressive nature of pancreatic ductal adenocarcinoma (PDAC) still remains unclear. Here we report evidence that the insulin-like growth factor-binding protein IGFBP2 acts as a potent oncogene to drive its extremely malignant character. We found that elevated IGFBP2 expression in primary tumors was associated with lymph node metastasis and shorter survival in patients with PDAC. Enforced expression of IGFBP2 promoted invasion and metastasis of PDAC cells in vitro and in vivo by inducing NF-?B-dependent epithelial-mesenchymal transition (EMT). Mechanistic investigations revealed that IGFBP2 induced the nuclear translocation and phosphorylation of the p65 NF-?B subunit through the PI3K/Akt/IKK? pathway. Conversely, enforced expression of PTEN blunted this signaling pathway and restored an epithelial phenotype to PDAC cells in the presence of overexpressed IGFBP2. Overall, our results identify IGFBP2 as a pivotal regulator of an EMT axis in PDAC, the activation of which is sufficient to confer the characteristically aggressive clinical features of this disease. Cancer Res; 76(22); 6543-54. ©2016 AACR.

SUBMITTER: Gao S

PROVIDER: S-EPMC5315491 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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IGFBP2 Activates the NF-κB Pathway to Drive Epithelial-Mesenchymal Transition and Invasive Character in Pancreatic Ductal Adenocarcinoma.

Gao Song S Sun Yan Y Zhang Xuebin X Hu Limei L Liu Yuexin Y Chua Corrine Yingxuan CY Phillips Lynette M LM Ren He H Fleming Jason B JB Wang Huamin H Chiao Paul J PJ Hao Jihui J Zhang Wei W

Cancer research 20160922 22

The molecular basis underlying the particularly aggressive nature of pancreatic ductal adenocarcinoma (PDAC) still remains unclear. Here we report evidence that the insulin-like growth factor-binding protein IGFBP2 acts as a potent oncogene to drive its extremely malignant character. We found that elevated IGFBP2 expression in primary tumors was associated with lymph node metastasis and shorter survival in patients with PDAC. Enforced expression of IGFBP2 promoted invasion and metastasis of PDAC ...[more]

PMID: 27659045

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Dataset Information

IGFBP2 Activates the NF-?B Pathway to Drive Epithelial-Mesenchymal Transition and Invasive Character in Pancreatic Ductal Adenocarcinoma.

Publications

IGFBP2 Activates the NF-κB Pathway to Drive Epithelial-Mesenchymal Transition and Invasive Character in Pancreatic Ductal Adenocarcinoma.

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