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Oncotarget. 2016 Nov 29;7(48):78859-78871. doi: 10.18632/oncotarget.12889.

Metastasis-suppressing NID2, an epigenetically-silenced gene, in the pathogenesis of nasopharyngeal carcinoma and esophageal squamous cell carcinoma.

Chai AW1, Cheung AK1, Dai W1, Ko JM1, Ip JC1, Chan KW2,3, Kwong DL1,4, Ng WT4,5, Lee AW1,4, Ngan RK4,6, Yau CC4,7, Tung SY4,8, Lee VH1,4, Lam AK9, Pillai S9, Law S2,10, Lung ML1,2,4.

Author information

1
Department of Clinical Oncology, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
2
Center for Cancer Research, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
3
Department of Pathology, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
4
Center for Nasopharyngeal Carcinoma Research, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
5
Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong (SAR), People's Republic of China.
6
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong (SAR), People's Republic of China.
7
Department of Oncology, Princess Margaret Hospital, Hong Kong (SAR), People's Republic of China.
8
Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong (SAR), People's Republic of China.
9
Department of Cancer Molecular Pathology, Griffith Medical School and Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
10
Department of Surgery, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.

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.

KEYWORDS:

Nidogen-2 (NID2); esophageal squamous cell carcinoma (ESCC); metastasis; nasopharyngeal carcinoma (NPC); promoter hypermethylation

PMID:
27793011
PMCID:
PMC5346683
DOI:
10.18632/oncotarget.12889
[Indexed for MEDLINE]
Free PMC Article

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