ANO1 amplification and expression in HNSCC with a high propensity for future distant metastasis and its functions in HNSCC cell lines

被引：126

作者：

Ayoub, C. ^{[1
]}

Wasylyk, C. ^{[1
]}

Li, Y. ^{[1
]}

Thomas, E. ^{[2
]}

Marisa, L. ^{[2
]}

Robe, A. ^{[1
]}

Roux, M. ^{[1
]}

Abecassis, J. ^{[3
]}

de Reynies, A. ^{[2
]}

Wasylyk, B. ^{[1
]}

机构：

[1] Inst Genet & Biol Mol & Cellulaire, CNRS, UMR UDS 7104, INSERM,U964, F-67404 Illkirch Graffenstaden, Graffenstaden, France

[2] Programme Cartes Ident Tumeurs CIT, F-75013 Paris, France

[3] Ctr Reg Lutte Canc Paul Strauss, Lab Biol Tumorale, F-67085 Strasbourg, France

来源：

BRITISH JOURNAL OF CANCER | 2010年 / 103卷 / 05期

关键词：

HNSCC; distant metastasis; ANO1; CaCC; cell movement; GASTROINTESTINAL STROMAL TUMORS; POOR-PROGNOSIS; CANCER-CELLS; ORAL-CANCER; NECK-CANCER; CYCLIN D1; CHROMOSOMAL-ABNORMALITIES; TRANSCRIPTOME ANALYSIS; HUMAN-PAPILLOMAVIRUS; GENE AMPLIFICATION;

D O I：

10.1038/sj.bjc.6605823

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is associated with poor survival. To identify prognostic and diagnostic markers and therapeutic targets, we studied ANO1, a recently identified calcium-activated chloride channel (CaCC). METHODS: High-resolution genomic and transcriptomic microarray analysis and functional studies using HNSCC cell line and CaCC inhibitors. RESULTS: Amplification and overexpression of genes within the 11q13 amplicon are associated with the propensity for future distance metastasis of HPV-negative HNSCC. ANO1 was selected for functional studies based on high correlations, cell surface expression and CaCC activity. ANO1 overexpression in cells that express low endogenous levels stimulates cell movement, whereas downregulation in cells with high endogenous levels has the opposite effect. ANO1 overexpression also stimulates attachment, spreading, detachment and invasion, which could account for its effects on migration. CaCC inhibitors decrease movement, suggesting that channel activity is required for the effects of ANO1. In contrast, ANO1 overexpression does not affect cell proliferation. INTERPRETATION: ANO1 amplification and expression could be markers for distant metastasis in HNSCC. ANO1 overexpression affects cell properties linked to metastasis. Inhibitors of CaCCs could be used to inhibit the tumourigenic properties of ANO1, whereas activators developed to increase CaCC activity could have adverse effects. British Journal of Cancer (2010) 103, 715-726. doi:10.1038/sj.bjc.6605823 www.bjcancer.com Published online 27 July 2010 (C) 2010 Cancer Research UK

引用

页码：715 / 726

页数：12

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