Oncotarget

Research Papers:

IκB-kinase-ε in the tumor microenvironment is essential for the progression of gastric cancer

Biao Geng, Chen Zhang, Chao Wang, Ying Che, Xianmin Mu, Jinshun Pan, Che Xu, Shi Hu, Jing Yang, Ting Zhao, Yue Xu, Yuanfang Lv, Hao Wen, Zheng Liu and Qiang You _

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Oncotarget. 2017; 8:75298-75307. https://doi.org/10.18632/oncotarget.20778

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Abstract

Biao Geng1,*, Chen Zhang1,*, Chao Wang2, Ying Che3, Xianmin Mu1, Jinshun Pan1, Che Xu1, Shi Hu1, Jing Yang1, Ting Zhao1, Yue Xu1, Yuanfang Lv1, Hao Wen2, Zheng Liu3 and Qiang You1,3,4,5

1Department of Biotherapy, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, China

2Department of Surgery, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, China

3Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, China

4Key Laboratory for Aging & Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, China

5Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu 211166, China

*These authors have contributed equally to this work

Correspondence to:

Qiang You, email: Qiang.You@live.com

Keywords: gastric cancer, IκB-kinase-ε, tumor-infiltrating lymphocytes, metastasis, prognostic biomarker

Received: June 14, 2017    Accepted: July 30, 2017    Published: September 08, 2017

ABSTRACT

The tumor microenvironment is critical for tumor growth and metastasis, but the underlying molecular mechanisms are poorly understood. Recent studies have shown that IκB-kinase-ε (IKKε) is involved in the proliferation and migration of certain cancers. However, the functional role of IKKε in the progression of gastric cancer (GC) remains unknown. In this study, we found that high levels of IKKε expression in GC tumors were correlated with more advanced disease and poor overall survival of patients. Silencing of IKKε effectively suppressed the migratory and invasive capabilities of human GC cells in vitro and tumorigenicity and metastasis in vivo. Further analysis revealed that IKKε was also highly expressed in tumor-infiltrating lymphocytes. Moreover, it was involved in tumor-infiltrating T-cell-mediated invasion and metastasis. Knockdown of IKKε elevated T-cell antitumor immunity. These findings suggest that IKKε may be a novel prognostic marker and a potential therapeutic target in human GCs.


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