Metastasis-suppressingNID2, an epigenetically-silenced gene, in the pathogenesis of nasopharyngeal carcinoma and esophageal squamous cell carcinoma
Author(s) -
Annie Wai Yeeng Chai,
Arthur Kwok Leung Cheung,
Wei Dai,
Josephine Mun Yee Ko,
Joseph Chok Yan Ip,
Kwok Wah Chan,
Dora LaiWan Kwong,
Wai Tong Ng,
Anne Wing Mui Lee,
Roger Kai Cheong Ngan,
Chun Chung Yau,
Stewart Y. Tung,
Victor Lee,
Alfred K. Lam,
Suja Pillai,
Simon Law,
Maria Li Lung
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.12889
Subject(s) - cancer research , metastasis , nasopharyngeal carcinoma , dna methylation , pathogenesis , extracellular matrix , mmp2 , methylation , cell migration , biology , medicine , cell , cancer , pathology , gene expression , gene , radiation therapy , microbiology and biotechnology , biochemistry , genetics
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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