@article{e445c5880a4d4294be3b803ff420bb32,
title = "IGFBP2 activates the NF-κB 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-κB-dependent epithelial-mesenchymal transition (EMT). Mechanistic investigations revealed that IGFBP2 induced the nuclear translocation and phosphorylation of the p65 NF-κB subunit through the PI3K/Akt/IKKb 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.",
author = "Song Gao and Yan Sun and Xuebin Zhang and Limei Hu and Yuexin Liu and Chua, {Corrine Yingxuan} and Phillips, {Lynette M.} and He Ren and Fleming, {Jason B.} and Huamin Wang and Chiao, {Paul J.} and Jihui Hao and Wei Zhang",
note = "Funding Information: We thank Dr. Anirban Maitra (Department of Pathology, MD Anderson Cancer Center, Houston, TX) for valuable discussion and input, Dr. Michael Karin (University of California, Los Angeles, Los Angeles, CA) for providing the IKK-null MEFs, Dr. Jared Burks (Flow Cytometry and Cellular Imaging Core Facility, MD Anderson Cancer Center, Houston, TX) for technical assistance, and Ms. Kathryn Hale (Department of Scientific Publications, MD Anderson Cancer Center, Houston, TX) for editing the manuscript. This study was partially supported by a grant from the U.S. NIH (U24CA143835) and the MD Anderson Cancer Center support grant (P30CA016672), a grant from the National Foundation for Cancer Research (W. Zhang), grants (81302082, 81172355) from the National Natural Science Foundation of China (J.H. Hao), and a grant (31301151) from the National Natural Science Foundation of China (S. Gao). W. Zhang is supported by the Hanes and Willies Family Professorship in Cancer at Wake Forest Baptist Medical Center. Publisher Copyright: {\textcopyright}2016 AACR.",
year = "2016",
month = nov,
day = "15",
doi = "10.1158/0008-5472.CAN-16-0438",
language = "English (US)",
volume = "76",
pages = "6543--6554",
journal = "Cancer research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "22",
}