title: Role of volume-regulated and calcium-activated anion channels in cell volume homeostasis, cancer and drug resistance.
abstract: Volume-regulated channels for anions (VRAC) / organic osmolytes (VSOAC) play essential roles in cell volume regulation and other cellular functions, e.g. proliferation, cell migration and apoptosis. LRRC8A, which belongs to the leucine rich-repeat containing protein family, was recently shown to be an essential component of both VRAC and VSOAC. Reduced VRAC and VSOAC activities are seen in drug resistant cancer cells. ANO1 is a calcium-activated chloride channel expressed on the plasma membrane of e.g., secretory epithelia. ANO1 is amplified and highly expressed in a large number of carcinomas. The gene, encoding for ANO1, maps to a region on chromosome 11 (11q13) that is frequently amplified in cancer cells. Knockdown of ANO1 impairs cell proliferation and cell migration in several cancer cells. Below we summarize the basic biophysical properties of VRAC, VSOAC and ANO1 and their most important cellular functions as well as their role in cancer and drug resistance.
authors.affiliation: a Department of Biology ; Section for Cell Biology and Physiology; University of Copenhagen ; Copenhagen , Denmark.
authors.forename: Else K
authors.initials: EK
authors.lastname: Hoffmann
authors.affiliation: a Department of Biology ; Section for Cell Biology and Physiology; University of Copenhagen ; Copenhagen , Denmark.
authors.forename: Belinda H
authors.initials: BH
authors.lastname: Sørensen
authors.affiliation: a Department of Biology ; Section for Cell Biology and Physiology; University of Copenhagen ; Copenhagen , Denmark.
authors.forename: Daniel P R
authors.initials: DP
authors.lastname: Sauter
authors.affiliation: a Department of Biology ; Section for Cell Biology and Physiology; University of Copenhagen ; Copenhagen , Denmark.
authors.forename: Ian H
authors.initials: IH
authors.lastname: Lambert
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D017209:Apoptosis; D048429:Cell Size; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D006706:Homeostasis; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D018118:Chloride Channels; C485976:LRRC8A protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins
keywords: LRRC8A; TMEM16A; VRAC; VSOAC; anoctamins; apoptotic volume decrease; regulatory volume decrease