dc.contributor.author | Fisch KM | |
dc.contributor.author | Sulzmaier FJ | |
dc.contributor.author | Barrie AM | |
dc.contributor.author | Chen XL | |
dc.contributor.author | Ojalill M | |
dc.contributor.author | Gyorffy B | |
dc.contributor.author | Taylor KN | |
dc.contributor.author | Xu GR | |
dc.contributor.author | McHale MT | |
dc.contributor.author | Uryu S | |
dc.contributor.author | Fu G | |
dc.contributor.author | Osterman CJD | |
dc.contributor.author | Anderson K | |
dc.contributor.author | Heino J | |
dc.contributor.author | Ozmadenci D | |
dc.contributor.author | Weaver DT | |
dc.contributor.author | Bean LM | |
dc.contributor.author | Cordasco EA | |
dc.contributor.author | Molinolo A | |
dc.contributor.author | Connolly DC | |
dc.contributor.author | Pachter JA | |
dc.contributor.author | Jean C | |
dc.contributor.author | Kolev VN | |
dc.contributor.author | Mark AM | |
dc.contributor.author | Kleinschmidt EG | |
dc.contributor.author | Jiang SL | |
dc.contributor.author | Li J | |
dc.contributor.author | Tancioni I | |
dc.contributor.author | Rappu P | |
dc.contributor.author | Stupack DG | |
dc.contributor.author | Schlaepfer DD | |
dc.date.accessioned | 2022-10-28T13:33:39Z | |
dc.date.available | 2022-10-28T13:33:39Z | |
dc.identifier.uri | https://www.utupub.fi/handle/10024/166029 | |
dc.description.abstract | Gene copy number alterations, tumor cell stemness, and the development of platinum chemotherapy resistance contribute to high-grade serous ovarian cancer (HGSOC) recurrence. Stem phenotypes involving Wnt-beta-catenin, aldehyde dehydrogenase activities, intrinsic platinum resistance, and tumorsphere formation are here associated with spontaneous gains in Kras, Myc and FAK (KMF) genes in a new aggressive murine model of ovarian cancer. Adhesion-independent FAK signaling sustained KMF and human tumorsphere proliferation as well as resistance to cisplatin cytotoxicity. Platinum-resistant tumorspheres can acquire a dependence on FAK for growth. Accordingly, increased FAK tyrosine phosphorylation was observed within HGSOC patient tumors surviving neo-adjuvant chemotherapy. Combining a FAK inhibitor with platinum overcame chemoresistance and triggered cell apoptosis. FAK transcriptomic analyses across knockout and reconstituted cells identified 135 targets, elevated in HGSOC, that were regulated by FAK activity and beta-catenin including Myc, pluripotency and DNA repair genes. These studies reveal an oncogenic FAK signaling role supporting chemoresistance. | |
dc.language.iso | en | |
dc.publisher | ELIFE SCIENCES PUBLICATIONS LTD | |
dc.title | FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy | |
dc.identifier.urn | URN:NBN:fi-fe2021042827686 | |
dc.relation.volume | 8 | |
dc.contributor.organization | fi=PÄÄT Biokemia|en=PÄÄT Biochemistry| | |
dc.contributor.organization-code | 2606201 | |
dc.converis.publication-id | 42614756 | |
dc.converis.url | https://research.utu.fi/converis/portal/Publication/42614756 | |
dc.identifier.eissn | 2050-084X | |
dc.identifier.jour-issn | 2050-084X | |
dc.okm.affiliatedauthor | Ojalill, Marjaana | |
dc.okm.affiliatedauthor | Heino, Jyrki | |
dc.okm.affiliatedauthor | Rappu, Pekka | |
dc.okm.discipline | 3111 Biolääketieteet | fi_FI |
dc.okm.discipline | 3111 Biomedicine | en_GB |
dc.okm.internationalcopublication | international co-publication | |
dc.okm.internationality | International publication | |
dc.okm.type | Journal article | |
dc.publisher.country | United Kingdom | en_GB |
dc.publisher.country | Britannia | fi_FI |
dc.publisher.country-code | GB | |
dc.relation.articlenumber | ARTN e47327 | |
dc.relation.doi | 10.7554/eLife.47327 | |
dc.relation.ispartofjournal | eLife | |
dc.year.issued | 2019 | |