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Whyworkingthenightshiftcanposeacancerrisk|MITNews
Inhumanandmototherorganim,a
circadianclockgovernedlight
regulatethetimingofkeapectof
humanphiolog,controllingcellular
activitieuchametaolimand
diviion.
Image:NationalCancerIntitute,Chritine
Daniloff/MIT
Whworkingthenighthiftcanpoeacancerrik
Newtudrevealalinketweencircadianclockdiruptionandtumorgrowth.
AnneTrafton|MITNewOffice
Jul28,2016
RLATD
Ahandfuloflargetudieofcancerrikfactorhavefoundthatworkingthenighthift,a
JackLa
nearl15percentofAmericando,ootthechanceofdevelopingcancer.MITiologit
havenowfoundalinkthatmaexplainthiheightenedrik.
KochIntitute
Inhumanandmototherorganim,acircadianclockgovernedlightregulatethetiming
ofkeapectofhumanphiolog,controllingcellularactivitieuchametaolimand
Departmentofiolog
diviion.Inatudofmice,theMITteamfoundthattwoofthegenethatcontrolcell
circadianrhthmalofunctionatumoruppreor.
choolofcience
Looftheetumoruppreor,eitherthroughgenedeletionordiruptionofthenormal
light/darkccle,allowtumortoecomemoreaggreive.
ARCHIV
Itdoentmatterhowoudirupttheclockothwa,loofiteemtodrive
tumorigenei,aThalePapagiannakopoulo,aformerpotdocatMITKochIntitutefor
IntegrativeCancerReearchandtheleadauthorofthetud,whichappearintheJul28
Fatmodelingof
cancermutation
iueofCellMetaolim.
TlerJack,directoroftheKochIntituteandtheDavidH.KochProfeorofiolog,ithe
papereniorauthor.
Newviewoftumor
evolution
reakingthecircadianclock
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Whyworkingthenightshiftcanposeacancerrisk|MITNews
Inhuman,thecentralcircadianclockilocatedintherainuprachiamaticnucleu(CN),
whichreceiveinformationaoutlightlevelfromtheretina.TheCNcommunicatethi
informationtocellintheodthroughhormoneandotherignalingmolecule.
Withincell,agenecalledmal1ireponileforturningonothergenethatcontrol
Thelinketweencircadianrhthm
andaging
circadianactivitie,includingonecalledPer2.Leveloftheproteinencodedtheegene
normallocillatethroughouttheda,utwhennormallight/darkcclearedirupted,thoe
ocillationdiappear.
Cellneedthelightcue,whichilikeareetuttonfortheclock.Whenouloethatcue,
ouloethenormalrhthminevercellinourod,aPapagiannakopoulo,whoinow
anaitantprofeorofpathologatNewYorkUniveritchoolofMedicine.
Heandhicolleagueetouttoinvetigateapoilelinketweencancerandtheegene,
inmicethataregeneticallengineeredtodevelopatpeoflungcancerknownanon-mall
celllungcancer.
Theeganexpoingthemicetotwodifferentlight/darkchedule.Onegroupofmice
livedwithanormalcheduleof12houroflightfollowed12hourofdarkne,whilethe
othermicewentontoajetlagchedule:vertwotothreeda,thewereexpoedtoan
additionaleighthouroflight.Thimimictheiologicalclockdiruptionthatoccurwhen
humanworknighthiftortravelthroughmultipletimezone.
Underthejetlagcenario,tumorgrewfaterandweremoreaggreivethanthoeinthe
micelivingwithanormallight/darkchedule.
Intheirnextetofexperiment,thereearcherkeptthemiceonanormallight/darkchedule
utknockedoutthegeneformal1andPer2.Inthoemice,tumorgrewfater,jutathe
didunderthejetlagcenario.
Ifoudirupttheegeneinevercelloftheod,thelightcuethatounormallreceive
donotappl,Papagiannakopouloa.Itawaoftakingamolecularhammerandjut
reakingthiclock.
Out-of-controlgrowth
mal1andPer2controlthetimingofproductionofacancer-promotingproteinknownacmc,owhenthoegenearedirupted,c-mcegintoaccumulate,purringanincreaein
cellmetaolimandproliferation.
C-mcturnonthiprogramthatmakecellproducemoremetaolite,morenutrient,
moreuildinglockfornewcell.Iteentialfortheailitofcelltoproliferate,
Papagiannakopouloa.
JoephTakahahi,chairoftheDepartmentofNeurocienceattheUniveritofTexa
outhweternMedicalCenter,athetudofferanimportantlinketweencancerand
circadianclockdfunction.
Thiworkiverclearanddefinitive,aTakahahi,whowanotinvolvedinthereearch.
Thatwhatweneedtoreallhowthatthecircadianclockmahaveimplicationforcancer
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Whyworkingthenightshiftcanposeacancerrisk|MITNews
andtumorprogreion.
TheMITreearcheraloanalzedhumanlungtumorampleandfoundmuchlowerlevelof
mal1andPer2geneexpreion,awellaotherkecircadianclockgene,inthetumor
thaninnormallungtiuefromtheamepatient.Themotaggreivetumorhadeven
lowerlevelofthoegene.
Papagiannakopouloinowinvetigatingwhethercancercellthathavearokenclock,for
examplethroughloofmal1andPer2,haveanweakneethatcouldeexploiteda
potentialdrugtarget.Healoplantotudhowcircadiandiruptionaffectothertpeof
cancer,includingpancreaticcancer.
ThereearchwafundedaNationalCancerIntituteCancerCenterupportCoreGrant,
theLungCancerReearchFoundation,andtheKochIntituteFrontierFund.
Topic:
Reearch
Cancer
iolog
KochIntitute
choolofcience
AoutThiWeite
ThiWeiteimaintainedtheMITNewOffice.
MITNewOfficeuilding11-400
MaachuettIntituteofTechnologCamridge,MA02139-4307
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