Oncotarget

Research Papers:

Elevated NIBP/TRAPPC9 mediates tumorigenesis of cancer cells through NFκB signaling

Yonggang Zhang, Shu Liu, Hong Wang, Wensheng Yang, Fang Li, Fan Yang, Daohai Yu, Frederick V. Ramsey, George P. Tuszyski and Wenhui Hu _

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Oncotarget. 2015; 6:6160-6178. https://doi.org/10.18632/oncotarget.3349

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Abstract

Yonggang Zhang1,*, Shu Liu2,*, Hong Wang1, Wensheng Yang1, Fang Li1, Fan Yang1, Daohai Yu3, Frederick V. Ramsey3, George P. Tuszyski1 and Wenhui Hu1

1 Department of Neuroscience, Temple University School of Medicine, Philadelphia, PA, USA

2 Department of Biotherapy, The Forth Affiliated Hospital, China Medical University, Shenyang, Liaoning, China

3 Department of Clinical Sciences, Temple University School of Medicine, Philadelphia, PA, USA

* These authors contributed equally to this work

Correspondence:

Wenhui Hu, email:

Keywords: NFκB, TRAPPC9, trans-Golgi network, cancer cells, tumorigenesis

Received: October 09, 2014 Accepted: January 20, 2015 Published: January 31, 2015

Abstract

Regulatory mechanisms underlying constitutive and inducible NFκB activation in cancer remain largely unknown. Here we investigated whether a novel NIK- and IKK2-binding protein (NIBP) is required for maintaining malignancy of cancer cells in an NFκB-dependent manner. Real-time polymerase chain reaction analysis of a human cancer survey tissue-scan cDNA array, immunostaining of a human frozen tumor tissue array and immunoblotting of a high-density reverse-phase cancer protein lysate array showed that NIBP is extensively expressed in most tumor tissues, particularly in breast and colon cancer. Lentivirus-mediated NIBP shRNA knockdown significantly inhibited the growth/proliferation, invasion/migration, colony formation and xenograft tumorigenesis of breast (MDA-MB-231) or colon (HCT116) cancer cells. NIBP overexpression in HCT116 cells promoted cell proliferation, migration and colony formation. Mechanistically, NIBP knockdown in cancer cells inhibited cytokine-induced activation of NFκB luciferase reporter, thus sensitizing the cells to TNFα-induced apoptosis. Endogenous NIBP bound specifically to the phosphorylated IKK2 in a TNFα-dependent manner. NIBP knockdown transiently attenuated TNFα-stimulated phosphorylation of IKK2/p65 and degradation of IκBα. In contrast, NIBP overexpression enhanced TNFα-induced NFκB activation, thus inhibiting constitutive and TNFα-induced apoptosis. Collectively, our data identified important roles of NIBP in promoting tumorigenesis via NFκΒ signaling, spotlighting NIBP as a promising target in cancer therapeutic intervention.


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