Research Papers:
Metastasis-suppressing NID2, an epigenetically-silenced gene, in the pathogenesis of nasopharyngeal carcinoma and esophageal squamous cell carcinoma
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Abstract
Annie Wai Yeeng Chai1, Arthur Kwok Leung Cheung1, Wei Dai1, Josephine Mun Yee Ko1, Joseph Chok Yan Ip1, Kwok Wah Chan2,3, Dora Lai-Wan Kwong1,4, Wai Tong Ng4,5, Anne Wing Mui Lee1,4, Roger Kai Cheong Ngan4,6, Chun Chung Yau4,7, Stewart Yuk Tung4,8, Victor Ho Fun Lee1,4, Alfred King-Yin Lam9, Suja Pillai9, Simon Law2,10, Maria Li Lung1,2,4
1Department of Clinical Oncology, The University of Hong Kong, Hong Kong (SAR), People’s Republic of China
2Center for Cancer Research, The University of Hong Kong, Hong Kong (SAR), People’s Republic of China
3Department of Pathology, The University of Hong Kong, Hong Kong (SAR), People’s Republic of China
4Center for Nasopharyngeal Carcinoma Research, The University of Hong Kong, Hong Kong (SAR), People’s Republic of China
5Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong (SAR), People’s Republic of China
6Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong (SAR), People’s Republic of China
7Department of Oncology, Princess Margaret Hospital, Hong Kong (SAR), People’s Republic of China
8Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong (SAR), People’s Republic of China
9Department of Cancer Molecular Pathology, Griffith Medical School and Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia
10Department of Surgery, The University of Hong Kong, Hong Kong (SAR), People’s Republic of China
Correspondence to:
Maria Li Lung, email: [email protected]
Keywords: Nidogen-2 (NID2), promoter hypermethylation, metastasis, nasopharyngeal carcinoma (NPC), esophageal squamous cell carcinoma (ESCC)
Received: June 21, 2016 Accepted: October 19, 2016 Published: October 25, 2016
ABSTRACT
Nidogen-2 (NID2) is a key component of the basement membrane that stabilizes the extracellular matrix (ECM) network. The aim of the study is to analyze the functional roles of NID2 in the pathogenesis of nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC). We performed genome-wide methylation profiling of NPC and ESCC and validated our findings using the methylation-sensitive high-resolution melting (MS-HRM) assay. Results showed that promoter methylation of NID2 was significantly higher in NPC and ESCC samples than in their adjacent non-cancer counterparts. Consistently, down-regulation of NID2 was observed in the clinical samples and cell lines of both NPC and ESCC. Re-expression of NID2 suppresses clonogenic survival and migration abilities of transduced NPC and ESCC cells. We showed that NID2 significantly inhibits liver metastasis. Mechanistic studies of signaling pathways also confirm that NID2 suppresses the EGFR/Akt and integrin/FAK/PLCγ metastasis-related pathways. This study provides novel insights into the crucial tumor metastasis suppression roles of NID2 in cancers.
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