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Leukaemia Inhibitory Factor (LIF) Inhibits Cancer Stem Cells Tumorigenic Properties through Hippo Kinases Activation in Gastric Cancer

hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorSEENEEVASSEN, Lornella
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorGIRAUD, Julie
hal.structure.identifierUniversidad de Costa Rica [UCR]
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorMOLINA-CASTRO, Silvia
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorSIFRÉ, Elodie
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorTIFFON, Camille
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorBEAUVOIT, Clémentine
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorSTAEDEL, Cathy
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorMÉGRAUD, Francis
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorLEHOURS, Philippe
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorMARTIN, Océane
hal.structure.identifierBioingénierie tissulaire [BIOTIS]
dc.contributor.authorBOEUF, Hélène
ORCID: 0000-0002-3006-8773
IDREF: 03205453X
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorDUBUS, Pierre
hal.structure.identifierBordeaux Research In Translational Oncology [Bordeaux] [BaRITOn]
dc.contributor.authorVARON, Christine
dc.date.accessioned2021-06-10T07:03:27Z
dc.date.available2021-06-10T07:03:27Z
dc.date.issued2020-08
dc.identifier.issn2072-6694
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/78916
dc.description.abstractEnCancer stem cells (CSCs) present chemo-resistance mechanisms contributing to tumour maintenance and recurrence, making their targeting of utmost importance in gastric cancer (GC) therapy. The Hippo pathway has been implicated in gastric CSC properties and was shown to be regulated by leukaemia inhibitory factor receptor (LIFR) and its ligand LIF in breast cancer. This study aimed to determine LIF's effect on CSC properties in GC cell lines and patient-derived xenograft (PDX) cells, which remains unexplored. LIF's treatment effect on CSC markers expression and tumoursphere formation was evaluated. The Hippo kinase inhibitor XMU-MP-1 and/or the JAK1 inhibitor Ruxolitinib were used to determine Hippo and canonical JAK/STAT pathway involvement in gastric CSCs' response to LIF. Results indicate that LIF decreased tumorigenic and chemo-resistant CSCs, in both GC cell lines and PDX cells. In addition, LIF increased activation of LATS1/2 Hippo kinases, thereby decreasing downstream YAP/TAZ nuclear accumulation and TEAD transcriptional activity. LIF's anti-CSC effect was reversed by XMU-MP-1 but not by Ruxolitinib treatment, highlighting the opposite effects of these two pathways downstream LIFR. In conclusion, LIF displays anti-CSC properties in GC, through Hippo kinases activation, and could in fine constitute a new CSCs-targeting strategy to help decrease relapse cases and bad prognosis in GC.
dc.language.isoen
dc.publisherMDPI
dc.subject.enJAK
dc.subject.enALDH
dc.subject.enCD44
dc.subject.enYAP
dc.subject.enLATS1/2
dc.subject.enGP190
dc.subject.engastric carcinoma
dc.subject.enRuxolitinib
dc.subject.enXMU-MP-1
dc.title.enLeukaemia Inhibitory Factor (LIF) Inhibits Cancer Stem Cells Tumorigenic Properties through Hippo Kinases Activation in Gastric Cancer
dc.typeArticle de revue
dc.identifier.doi10.3390/cancers12082011
dc.subject.halSciences du Vivant [q-bio]
bordeaux.journalCancers
bordeaux.page2011
bordeaux.volume12
bordeaux.hal.laboratoriesBioingénierie Tissulaire (BioTis) - U1026*
bordeaux.issue8
bordeaux.institutionCNRS
bordeaux.institutionINSERM
bordeaux.institutionCHU de Bordeaux
bordeaux.institutionInstitut Bergonié
bordeaux.peerReviewedoui
hal.identifierhal-03038893
hal.version1
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-03038893v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Cancers&rft.date=2020-08&rft.volume=12&rft.issue=8&rft.spage=2011&rft.epage=2011&rft.eissn=2072-6694&rft.issn=2072-6694&rft.au=SEENEEVASSEN,%20Lornella&GIRAUD,%20Julie&MOLINA-CASTRO,%20Silvia&SIFR%C3%89,%20Elodie&TIFFON,%20Camille&rft.genre=article


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