Crosstalk between the TNF and IGF pathways enhances NF-κB activation and signaling in cancer cells. Issue 5 (October 2015)

• Record Type: Journal Article
• Authors: Li, Shun; Pinard, Maxime; Wang, Yunling; Yang, Long; Lin, Rongtuan; Hiscott, John; Su, Bing; Brodt, Pnina
• Is Part Of: Growth hormone & IGF research. Volume 25:Issue 5(2015:Oct.)
• Page Start: 253
• Page End: 261
• Publication Date: 2015-10
• Subjects: Growth regulators -- Periodicals; Growth -- Regulation -- Periodicals; Somatomedin -- Periodicals; Somatomedins -- Periodicals; Growth Hormone -- Periodicals; Growth Substances -- Periodicals; Croissance -- Régulation -- Périodiques; Croissance -- Régulateurs -- Périodiques; Somatotrophine -- Périodiques; Somatomédine -- Périodiques; Growth -- Regulation; Growth regulators; Electronic journals; Periodicals; Electronic journals; 612.4
• DOI: 10.1016/j.ghir.2015.07.008
• Languages: English
• ISSNs: 1096-6374

Abstract

<abstract abstract-type="author" id="ab0005"> <title id="st0005">Abstract</title> <sec> <title id="st0010">Background</title> <p id="sp0005">The receptor for type I insulin like growth factor (IGF-IR) and NFκB signaling both play essential roles in cancer initiation and progression but relatively little is known about possible crosstalk between these pathways. We have shown that the IGF-IR could rescue lung and colon carcinoma cells from Tumor necrosis factor -α (ΤΝF-α)-induced apoptosis by activating autocrine, pro-survival IL-6/gp130/STAT3 signaling, suggesting that IGF-IR expression could alter NF-κB signaling that is required for transcriptional activation of IL-6.</p> </sec> <sec> <title id="st0015">Objective</title> <p id="sp0010">Here we sought to determine if and how IGF-IR signaling promotes TNF-α-induced NFκB activation.</p> </sec> <sec> <title id="st0070">Design</title> <p id="sp0020">We used lung carcinoma M-27 and colon carcinoma MC-38 cells to investigate IGF-IR-induced changes to the IKK/IκBα/NFκB pathway by a combination of qPCR, Western blotting, electrophoretic mobility shift assay, a reporter assay and gene silencing.</p> </sec> <sec> <title id="st0020">Results</title> <p id="sp0025">We show that in the presence of increased IGF-IR expression or activation levels, nuclear translocation of NFκB in response to TNF-α was enhanced in lung and colon carcinoma cells and this was due to accelerated phosphorylation and degradation of IκBα. This effect was AKT-dependent and mediated via mitogen-activated protein kinase kinase kinase 3(MEKK3) activation.</p> </sec> <sec> <title id="st0025">Conclusion</title> <p id="sp0035">The results suggest that ligand-mediated activation of IGF-IR alters NF-κB signaling in cancer cells in an AKT/MEKK3-dependent manner and that temporal aspects of NF-κB activation can regulate the cytokine profile of the tumor cells and thereby, their interaction with the microenvironment.</p> </sec> </abstract>