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


CONCLUSIONS
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.
Ayoub
C
C
Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104 CNRS UDS - U 964 INSERM, 1 Rue Laurent Fries, BP 10142, 67404 Illkirch cedex, Graffenstaden, France.
Wasylyk
C
C
Li
Y
Y
Thomas
E
E
Marisa
L
L
Robé
A
A
Roux
M
M
Abecassis
J
J
de Reyniès
A
A
Wasylyk
B
B
D000075369:Anoctamin-1; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018118:Chloride Channels; D018450:Disease Progression; D005784:Gene Amplification; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics*
C476213:ANO1 protein, human; D000075369:Anoctamin-1; D018118:Chloride Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins