title: Metastasis-suppressing NID2, an epigenetically-silenced gene, in the pathogenesis of nasopharyngeal carcinoma and esophageal squamous cell carcinoma.
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.
authors: Department of Clinical Oncology, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors: Annie Wai Yeeng
authors: AW
authors: Chai
authors: Department of Clinical Oncology, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors: Arthur Kwok Leung
authors: AK
authors: Cheung
authors: Department of Clinical Oncology, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors: Wei
authors: W
authors: Dai
authors: Department of Clinical Oncology, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors: Josephine Mun Yee
authors: JM
authors: Ko
authors: Department of Clinical Oncology, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors: Joseph Chok Yan
authors: JC
authors: Ip
authors: Center for Cancer Research, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Department of Pathology, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors: Kwok Wah
authors: KW
authors: Chan
authors: Department of Clinical Oncology, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Center for Nasopharyngeal Carcinoma Research, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors: Dora Lai-Wan
authors: DL
authors: Kwong
authors: Center for Nasopharyngeal Carcinoma Research, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong (SAR), People's Republic of China.
authors: Wai Tong
authors: WT
authors: Ng
authors: Department of Clinical Oncology, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Center for Nasopharyngeal Carcinoma Research, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors: Anne Wing Mui
authors: AW
authors: Lee
authors: Center for Nasopharyngeal Carcinoma Research, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong (SAR), People's Republic of China.
authors: Roger Kai Cheong
authors: RK
authors: Ngan
authors: Center for Nasopharyngeal Carcinoma Research, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Department of Oncology, Princess Margaret Hospital, Hong Kong (SAR), People's Republic of China.
authors: Chun Chung
authors: CC
authors: Yau
authors: Center for Nasopharyngeal Carcinoma Research, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong (SAR), People's Republic of China.
authors: Stewart Yuk
authors: SY
authors: Tung
authors: Department of Clinical Oncology, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Center for Nasopharyngeal Carcinoma Research, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors: Victor Ho Fun
authors: VH
authors: Lee
authors: Department of Cancer Molecular Pathology, Griffith Medical School and Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
authors: Alfred King-Yin
authors: AK
authors: Lam
authors: Department of Cancer Molecular Pathology, Griffith Medical School and Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia.
authors: Suja
authors: S
authors: Pillai
authors: Center for Cancer Research, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Department of Surgery, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors: Simon
authors: S
authors: Law
authors: Department of Clinical Oncology, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Center for Cancer Research, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.|Center for Nasopharyngeal Carcinoma Research, The University of Hong Kong, Hong Kong (SAR), People's Republic of China.
authors: Maria Li
authors: ML
authors: Lung
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D066246:ErbB Receptors / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D051966:Phospholipase C gamma / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D016023:Integrins; C114729:NID2 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051966:Phospholipase C gamma
keywords: Nidogen-2 (NID2); esophageal squamous cell carcinoma (ESCC); metastasis; nasopharyngeal carcinoma (NPC); promoter hypermethylation