title: Ion channels and transporters in metastasis.
abstract: An elaborate interplay between ion channels and transporters, components of the cytoskeleton, adhesion molecules, and signaling cascades provides the basis for each major step of the metastatic cascade. Ion channels and transporters contribute to cell motility by letting through or transporting ions essential for local Ca2+, pH and--in cooperation with water permeable aquaporins--volume homeostasis. Moreover, in addition to the actual ion transport they, or their auxiliary subunits, can display non-conducting activities. They can exert kinase activity in order to phosphorylate cytoskeletal constituents or their associates. They can become part of signaling processes by permeating Ca2+, by generating local pH-nanodomains or by being final downstream effectors. A number of channels and transporters are found at focal adhesions, interacting directly or indirectly with proteins of the extracellular matrix, with integrins or with components of the cytoskeleton. We also include the role of aquaporins in cell motility. They drive the outgrowth of lamellipodia/invadopodia or control the number of β1 integrins in the plasma membrane. The multitude of interacting ion channels and transporters (called transportome) including the associated signaling events holds great potential as therapeutic target(s) for anticancer agents that are aimed at preventing metastasis. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.
authors.affiliation: Department of Gastroenterology, Hannover Medical School, Hannover, Germany. Electronic address: Stock.Christian@mh-hannover.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Stock
authors.affiliation: Institute of Physiology II, University of Münster, Robert-Koch-Str. 27b, D-48149 Münster, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Schwab
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D020346:Aquaporins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017136:Ion Transport; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D020346:Aquaporins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D007473:Ion Channels; D026901:Membrane Transport Proteins; D002118:Calcium
keywords: Adhesion; Cell-cell contact; Epithelial-mesenchymal transition; Extravasation; Invasion; Transportome