Eag and HERG potassium channels as novel therapeutic targets in cancer.docVIP

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Eag and HERG potassium channels as novel therapeutic targets in cancer.doc

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Eag and HERG potassium channels as novel therapeutic targets in cancer

Asheretal.WorldJournalofSurgicalOncology2010,8:113 /content/8/1/113 WORLD JOURNAL OF SURGICAL ONCOLOGY REVIEW OpenAccess EagandHERGpotassiumchannelsasnovel therapeutictargetsincancer VirenAsher ,HeidiSowter ,RobertShaw,AnishBali ,RaheelaKhan5 1* 2 3 4 Abstract Voltagegatedpotassiumchannelshavebeenextensivelystudiedinrelationtocancer.Inthisreview,wewillfocus ontheroleoftwopotassiumchannels,Etherà-go-go(Eag),Humanetherà-go-gorelatedgene(HERG),incancer andtheirpotentialtherapeuticutilityinthetreatmentofcancer.EagandHERGareexpressedincancersofvarious organsandhavebeenimplicatedincellcycleprogressionandproliferationofcancercells.Inhibitionofthese channelshasbeenshowntoreduceproliferationbothinvitroandvivostudiesidentifyingpotassiumchannel modulatorsasputativeinhibitorsoftumourprogression.Eagchannelsinviewoftheirrestrictedexpressioninnor- maltissuemayemergeasnoveltumourbiomarkers. Introduction In particular the role of voltage gated K+ channels in Cancerisoneofthemajorkillersthroughouttheworld. cancer, has been reviewed in several excellent publica- Itisestimatedthatatotalof1,529,560newcancercases tions[2,10,11].Thisreviewwillfocusspecificallyonthe + and569,490deathsfromcancerwilloccurintheUnited Eag and HERG voltage gated K channels with their Statesin2010[1].Thereisincreasingevidencethation potentialtherapeuticapplicationsincancer. channelsareinvolvedinvariousprocessescharacteristic of cancer cells such as uncontrolled cell proliferation, Historicalperspective migrationandsurvivalinhypoxicconditions[2]. The Eag gene, present on locus 50 of the X chromo- Ion channels are integral membrane proteins that some of the fruitfly Drosophila melanogaster , is a mediate the transfer of ions through the hydrophobic mutant of the Shaker gene [12], so called since flies lipidbilayerofthecellmembrane.Theyplayanimpor- afflicted with this mutation exhibited slow, rhythmic tantroleinavarietyoffunctionsthatrangefromnerve/ shaking of the legs