IκB-kinase-ε in the tumor microenvironment is essential for the progression of gastric cancer
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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
Qiang You, email: [email protected]
Keywords: gastric cancer, IκB-kinase-ε, tumor-infiltrating lymphocytes, metastasis, prognostic biomarker
Received: June 14, 2017 Accepted: July 30, 2017 Published: September 08, 2017
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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