Matches in SemOpenAlex for { <https://semopenalex.org/work/W2927317845> ?p ?o ?g. }
- W2927317845 abstract "Abstract Gene copy number changes, cancer stem cell (CSC) increases, and platinum chemotherapy resistance contribute to poor prognosis in patients with recurrent high grade serous ovarian cancer (HGSOC). CSC phenotypes involving Wnt-β-catenin and aldehyde dehydrogenase activities, platinum resistance, and tumor initiating frequency are here associated with spontaneous genetic gains, including genes encoding K RAS , M YC and F AK , in a new murine model of ovarian cancer (KMF). Noncanonical FAK signaling was sufficient to sustain human and KMF tumorsphere proliferation, CSC survival, and platinum resistance. Increased FAK tyrosine phosphorylation occurred in HGSOC patient tumors surviving neo-adjuvant platinum and paclitaxel chemotherapy and platinum resistant tumorspheres acquired FAK dependence for growth. Importantly, combining a pharmacologic FAK inhibitor with platinum overcame chemoresistance and triggered apoptosis in vitro and in vivo . Knockout, rescue, genomic and transcriptomic analyses collectively identified more than 400 genes regulated along a FAK/β-catenin/Myc axis impacting stemness and DNA repair in HGSOC, with 66 genes gained in a majority of Cancer Genome Atlas samples. Together, these results support combinatorial testing of FAK inhibitors for the treatment of recurrent ovarian cancer. Graphical Summary Key Points High grade serous ovarian carcinoma tumors contain PTK2 (FAK) 8q24.3 gains associated with prognostic differences. KMF, a new murine ovarian cancer model with K -Ras, M yc, and F AK gene gains and intrinsic platinum resistance. FAK activation in tumors surviving platinum chemotherapy promotes cancer stem cell survival. FAK facilitates a β-catenin-Myc signaling axis controlling gene expression supporting platinum resistance. FAK activity is essential for KMF tumor growth and is a targetable cellular adaptation of platinum resistance." @default.
- W2927317845 created "2019-04-11" @default.
- W2927317845 creator A5001879806 @default.
- W2927317845 creator A5006342431 @default.
- W2927317845 creator A5006498849 @default.
- W2927317845 creator A5009456354 @default.
- W2927317845 creator A5011219662 @default.
- W2927317845 creator A5017389050 @default.
- W2927317845 creator A5022292989 @default.
- W2927317845 creator A5025541997 @default.
- W2927317845 creator A5029159238 @default.
- W2927317845 creator A5039178057 @default.
- W2927317845 creator A5040691385 @default.
- W2927317845 creator A5045971507 @default.
- W2927317845 creator A5049731648 @default.
- W2927317845 creator A5052883326 @default.
- W2927317845 creator A5056164616 @default.
- W2927317845 creator A5057799963 @default.
- W2927317845 creator A5058012640 @default.
- W2927317845 creator A5058181019 @default.
- W2927317845 creator A5058720808 @default.
- W2927317845 creator A5059145284 @default.
- W2927317845 creator A5059504870 @default.
- W2927317845 creator A5063520642 @default.
- W2927317845 creator A5064292507 @default.
- W2927317845 creator A5068538895 @default.
- W2927317845 creator A5071664080 @default.
- W2927317845 creator A5073675187 @default.
- W2927317845 creator A5074838425 @default.
- W2927317845 creator A5079482220 @default.
- W2927317845 creator A5081651835 @default.
- W2927317845 creator A5089337746 @default.
- W2927317845 creator A5090973852 @default.
- W2927317845 date "2019-03-30" @default.
- W2927317845 modified "2023-10-17" @default.
- W2927317845 title "FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy" @default.
- W2927317845 cites W1695398347 @default.
- W2927317845 cites W1781764024 @default.
- W2927317845 cites W1902804987 @default.
- W2927317845 cites W1984940900 @default.
- W2927317845 cites W1997338647 @default.
- W2927317845 cites W2004976275 @default.
- W2927317845 cites W2005042183 @default.
- W2927317845 cites W2008034243 @default.
- W2927317845 cites W2017975901 @default.
- W2927317845 cites W2022207080 @default.
- W2927317845 cites W2028667039 @default.
- W2927317845 cites W2044423100 @default.
- W2927317845 cites W2044895919 @default.
- W2927317845 cites W2050946558 @default.
- W2927317845 cites W2059407064 @default.
- W2927317845 cites W2071756286 @default.
- W2927317845 cites W2111900617 @default.
- W2927317845 cites W2112566803 @default.
- W2927317845 cites W2112686792 @default.
- W2927317845 cites W2113324742 @default.
- W2927317845 cites W2123696077 @default.
- W2927317845 cites W2148512375 @default.
- W2927317845 cites W2161103689 @default.
- W2927317845 cites W2164953703 @default.
- W2927317845 cites W2171249989 @default.
- W2927317845 cites W2258963753 @default.
- W2927317845 cites W2269087069 @default.
- W2927317845 cites W2329307756 @default.
- W2927317845 cites W2341594612 @default.
- W2927317845 cites W2438447375 @default.
- W2927317845 cites W2464880876 @default.
- W2927317845 cites W2513362995 @default.
- W2927317845 cites W2523826139 @default.
- W2927317845 cites W2528438395 @default.
- W2927317845 cites W2556570155 @default.
- W2927317845 cites W2577009212 @default.
- W2927317845 cites W2580617915 @default.
- W2927317845 cites W2588029840 @default.
- W2927317845 cites W2591535357 @default.
- W2927317845 cites W2594519469 @default.
- W2927317845 cites W2624467319 @default.
- W2927317845 cites W2626577233 @default.
- W2927317845 cites W2768887441 @default.
- W2927317845 cites W2769136370 @default.
- W2927317845 cites W2774205189 @default.
- W2927317845 cites W2774939642 @default.
- W2927317845 cites W2781525129 @default.
- W2927317845 cites W2782986679 @default.
- W2927317845 cites W2789525187 @default.
- W2927317845 cites W2795867722 @default.
- W2927317845 cites W2796153225 @default.
- W2927317845 cites W2796307849 @default.
- W2927317845 cites W2799723921 @default.
- W2927317845 cites W2806421539 @default.
- W2927317845 cites W2899760200 @default.
- W2927317845 cites W2905911461 @default.
- W2927317845 cites W4211203170 @default.
- W2927317845 doi "https://doi.org/10.1101/594184" @default.
- W2927317845 hasPublicationYear "2019" @default.
- W2927317845 type Work @default.
- W2927317845 sameAs 2927317845 @default.
- W2927317845 citedByCount "0" @default.
- W2927317845 crossrefType "posted-content" @default.
- W2927317845 hasAuthorship W2927317845A5001879806 @default.