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FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy [ID8 and ID8-IP / KMF cells]

ABSTRACT: FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy [ID8 and ID8-IP / KMF cells]

PROVIDER: PRJNA530133 | ENA |

REPOSITORIES: ENA

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FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy [ID8 and ID8-IP / KMF cells]

Project description: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-b-catenin and aldehyde dehydrogenase activities, platinum resistance, and tumor initiating frequency are here associated with spontaneous genetic gains, including genes encoding KRAS, MYC and FAK, 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/b-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.

2019-07-01 | GSE129097 | GEO

FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy [KMF parental, KMF clone KT13 (FAK-/-), KT13 + GFP-FAK, KT13 + GFP-FAK R454, and KT13 + deltaGSK beta-catenin]

2019-07-01 | GSE129098 | GEO

FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy

Project description:FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy

| PRJNA530129 | ENA

Project description:FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy [KMF parental, KMF clone KT13 (FAK-/-), KT13 + GFP-FAK, KT13 + GFP-FAK R454, and KT13 + deltaGSK beta-catenin]

| PRJNA530132 | ENA

Effect of FAK K454R mutation or knockout on composition of extracellular matrix and associated membrane proteins in 3D culture of ID8 mouse ovarian surface epithelial cells

Project description:ID8 mouse ovarian surface epithelial cells with or without K454R mutant and knockout of FAK were cultured as spheroid cultures. The cells were hypotonically lysed and washed out, and the insoluble material was analyzed by LC-MS/MS.

2019-08-30 | PXD013062 | Pride

FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy.

Project description: Not available

| S-EPMC6721800 | biostudies-literature

FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-07-01 | GSE129099 | GEO

ID8 whole exome sequence

Project description:The data in this submission relate to whole exome sequencing from murine ovarian cancer cell line ID8. All sequencing was performed by Beckman Coulter Genomics, Grenoble, France in February 2013.

2018-03-31 | E-MTAB-4663 | biostudies-arrayexpress

RNA-seq analysis of ID8 ovarian cancer cells after harvest from malignant ascites

Project description:Sequencing of mRNA from ID8 tumor cells and ID8 tumor cells harvested from ascites of mice 11 weeks after intra peritoneal inoculation show acquisition of cancer stem cell-like features in ascitic tumor cells.

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ID8 whole exome sequence

Project description:ID8 whole exome sequence

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