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dc.creatorSeeneevassen, Lornella
dc.creatorGiraud, Julie
dc.creatorMolina Castro, Silvia Elena
dc.creatorSifré, Elodie
dc.creatorTiffon, Camille
dc.creatorBeauvoit, Clémentine
dc.creatorStaedel, Cathy
dc.creatorMégraud, Francis
dc.creatorLethours, Philippe
dc.creatorMartin, Océane C.B.
dc.creatorBoeuf, Hélène
dc.creatorDubus, Pierre
dc.creatorVaron, Christine
dc.date.accessioned2021-10-21T19:50:53Z
dc.date.available2021-10-21T19:50:53Z
dc.date.issued2020
dc.identifier.citationhttps://www.mdpi.com/2072-6694/12/8/2011es_ES
dc.identifier.issn2072-6694
dc.identifier.urihttps://hdl.handle.net/10669/84667
dc.description.abstractCancer 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.es_ES
dc.description.sponsorshipMinistry of Tertiary Education, Research and Innovation/[]//Franciaes_ES
dc.description.sponsorshipLigue Nationale Française Contre le Cancer (French National League against Cancer)/[]//Franciaes_ES
dc.description.sponsorshipUniversidad de Costa Rica/[]/UCR/Costa Ricaes_ES
dc.description.sponsorshipMinisterio de Ciencia, Innovación, Tecnología y Telecomunicaciones/[]/MICITT/Costa Ricaes_ES
dc.description.sponsorshipFrench National Cancer Institute/[PLBio 2014-152]/INCa/Franciaes_ES
dc.language.isoenges_ES
dc.sourceCancers (Basel), vol.12(8), pp.1-24es_ES
dc.subjectGastric carcinomaes_ES
dc.subjectGP190es_ES
dc.subjectLATS1/2es_ES
dc.subjectYAPes_ES
dc.subjectCD44es_ES
dc.subjectALDHes_ES
dc.subjectJAKes_ES
dc.subjectRuxolitinibes_ES
dc.subjectXMU-MP-1es_ES
dc.titleLeukaemia Inhibitory Factor (LIF) inhibits cancer stem cells tumorigenic properties through hippo kinases activation in gastric canceres_ES
dc.typeartículo científicoes_ES
dc.identifier.doi10.3390/cancers12082011
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA)es_ES


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