Done With TheBirinapantGossip? We're At This Website On Your Behalf!


Post
DOI:10.1038/ncomms9388
OPEN
Received16Jul2015|Accepted17Aug2015|Published24Sep2015
PTENregulatesciliathroughDishevelled


Articles
Integrinendosomalsignallingsuppressesanoikis
JonnaAlanko
1,2
,AnjaMai,GuillaumeJacquemet,KristineSchauer,RiinaKaukonen,MarkkuSaari Done With The NumerousRucaparibAnnouncements? We're There For Your Needs ,
1 1 3 1 1,2
BrunoGoud
3
andJohannaIvaska
1,2,4,5
Integrin-containingfocaladhesionstransmitextracellularsignalsacrosstheplasmamembranetomodulatecelladhesion,
signallingandsurvival.Althoughintegrinsareknowntoundergocontinuousendo/exocytictraf?c,thepotentialimpactof
endocytictraf?conintegrin-inducedsignalsisunknown.Here,wedemonstratethatintegrinsignallingisnotrestrictedto
cell�CECMadhesionsandidentifyanendosomalsignallingplatformthatsupportsintegrinsignallingawayfromtheplasma
membrane.

Weshowthatactivefocaladhesionkinase(FAK),anestablishedmarkerofintegrin�CECMdownstreamsignalling,
localizeswithactiveintegrinsonendosomes.Integrinendocytosispositivelyregulatesadhesion-inducedFAKactivation,whichis
earlyendosomeantigen-1andsmallGTPaseRab21dependent.FAKbindsdirectlytopuri?edendosomesandbecomesactivated
onthem,suggestingaroleforendocytosisinenhancingdistinctintegrindownstreamsignallingevents.Eventually,endosomal
integrinsignallingcontributestocancer-relatedprocessessuchasanoikisresistance,anchorageindependenceandmetastasis.
Integrins
are
heterodimeric
cell-surface
adhesion
receptors
correlates Fed Up With The NumerousRucaparibUpdates? We're At This Site Available For You! with decreased anoikis sensitivity in usual cells and
functioning as integrators of the extracellular matrix (ECM)- anchorage-independentgrowthandmetastasisinbreastcancercells.


driven cues, the Done With TheRucaparibReports? We're At This Site Just For You!! cellular cytoskeleton plus the cellular signalling
apparatus
1
. On adhesion, integrins trigger the formation of plasma
membrane-proximal significant mechanosensing and signal-transmitting ActiveFAKlocalizestointegrin-containingendosomes
protein clusters depicted as ��adhesomes�� . Additionally, integrins Cell�CECMadhesionandactivationofintegrinsignallingisnecessary
undergo frequent endocytic tra?c to facilitate focal adhesion for cell survival, di?erentiation and developmental processes
turnover,cellmigration,invasionandcytokinesis.Forotherreceptor Integrin endocytosis o?ers an e?cient program to control integrin
Outcomes
2,3
13,14
.


4
systemsitiswellestablishedthatendocyticmembranetra?cregulates heterodimeravailabilityatthecellsurfaceandthusthespecificECM-
bioavailability of cell-surface molecules and as a result the intensity induced cellular response throughout processes for example cell migration
and/or specificity of receptor-initiated signals
integrinsandtheirligandshavebeendetectedinendosomes
increasedintegrinrecyclingtotheplasmamembranecontributesto established marker of integrin�CECM engagement and downstream
enhancedsignallingofco-tra?ckedreceptortyrosinekinases weusedananti-pFAK-Y397antibodytovisualizeintegrin
5,6
. Whilst active andtumourcellinvasion
and
15,16
.AsFAKrecruitmenttofocaladhesions
and subsequent Tyr 397 autophosphorylation (pFAK-Y397) is an
7�C9
ten,1