Role of anoctamins in cancer and apoptosis.
Anoctamin 1 (TMEM16A, Ano1) is a recently identified Ca(2+)-activated chloride channel and a member of a large protein family comprising 10 paralogues. Before Ano1 was identified as a chloride channel protein, it was known as the cancer marker DOG1. DOG1/Ano1 is expressed in gastrointestinal stromal tumours (GIST) and particularly in head and neck squamous cell carcinoma, at very high levels never detected in other tissues. It is now emerging that Ano1 is part of the 11q13 locus, amplified in several types of tumour, where it is thought to augment cell proliferation, cell migration and metastasis. Notably, Ano1 is upregulated through histone deacetylase (HDAC), corresponding to the known role of HDAC in HNSCC. As Ano1 does not enhance proliferation in every cell type, its function is perhaps modulated by cell-specific factors, or by the abundance of other anoctamins. Thus Ano6, by regulating Ca(2+)-induced membrane phospholipid scrambling and annexin V binding, supports cellular apoptosis rather than proliferation. Current findings implicate other cellular functions of anoctamins, apart from their role as Ca(2+)-activated Cl(-) channels.
Institut für Physiologie, Universität Regensburg, , Universitätsstraße 31, Regensburg 93053, Germany.
Podchanart
P
Wanitchakool
Luisa
L
Wolf
Gudrun E
GE
Koehl
Lalida
L
Sirianant
Rainer
R
Schreiber
Sucheta
S
Kulkarni
Umamaheswar
U
Duvvuri
Karl
K
Kunzelmann
D000075369:Anoctamin-1; D000075368:Anoctamins; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D053823:Hedgehog Proteins / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D049294:Phospholipid Transfer Proteins / Q000378:metabolism / Q000502:physiology*
C476213:ANO1 protein, human; C555078:ANO6 protein, human; D000075369:Anoctamin-1; D000075368:Anoctamins; D018118:Chloride Channels; D053823:Hedgehog Proteins; D009363:Neoplasm Proteins; D049294:Phospholipid Transfer Proteins; D006655:Histone Deacetylases; D002118:Calcium
TMEM16A; TMEM16F; anoctamin 1; anoctamin 6; cancer; head and neck stromal cell carcinoma