Autophagyincolorectalcancer:Animportantswitchfromphysiologytopathology

摘要： Colorectalcancer(CRC)remainsaleadingcauseofcancerdeathinbothmenandwomenworldwide.AmongthefactorsandmechanismsthatareinvolvedinthemultifactorialetiologyofCRC,autophagyisanimportanttransformationalswitchthatoccurswhenacellshiftsfromnormaltomalignant.Inrecentyears,multiplehypotheseshavebeenconsideredregardingtheautophagymechanismsthatareinvolvedincancer.Thecurrentlyacceptedhypothesisisthatautophagyhasdualandcontradictoryrolesincarcinogenesis,buttheprecisemechanismsleadingtoautophagyincancerarenotyetfullydefinedandseemtobecontextdependent.Autophagyisasurveillancemechanismusedbynormalcellsthatprotectsthemfromthetransformationtomalignancybyremovingdamagedorganellesandaggregatedproteinsandbyreducingreactiveoxygenspecies,mitochondrialabnormalitiesandDNAdamage.However,autophagyalsosupportstumorformationbypromotingaccesstonutrientsthatarecriticaltothemetabolismandgrowthoftumorcellsandbyinhibitingcellulardeathandincreasingdrugresistance.AutophagystudiesinCRChavefocusedonseveralmolecules,mainlymicrotubule-associatedprotein1lightchain3,beclin1,andautophagyrelated5,withconflictingresults.BeneficialeffectswereobservedforsomeagentsthatmodulateautophagyinCRCeitheraloneor,moreoften,incombinationwithotheragents.Moreextensivestudiesareneededinthefuturetoclarifytherolesofautophagy-relatedgenesandmodulatorsincolorectalcarcinogenesis,andtodeveloppotentialbeneficialagentsfortheprognosisandtreatmentofCRC. ... （共14頁）