GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE129097 Query DataSets for GSE129097
Status Public on Jul 01, 2019
Title FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy [ID8 and ID8-IP / KMF cells]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
Overall design mRNA profiles of ID8 and ID8-IP / KMF cells were generated in triplicate using an Illumina NovaSeq 6000 Sequencing System
Contributor(s) Díaz Osterman CJ, Ozmadenci D, Kleinschmidt EG, Taylor KN, Barrie AM, Jiang S, Bean LM, Sulzmaier FJ, Jean C, Tancioni I, Anderson K, Uryu S, Cordasco EA, Li J, Chen XL, Fu G, Ojalill M, Rappu P, Heino J, Mark AM, Xu G, Fisch KM, Kolev VN, Weaver DT, Pachter JA, Győrffy B, McHale MT, Connolly DC, Molinolo A, Stupack DG, Schlaepfer DD
Citation(s) 31478830
Submission date Apr 01, 2019
Last update date Sep 11, 2019
Contact name David D Schlaepfer
Phone 858822344
Organization name UCSD
Department Moores Cancer Center
Lab Gynecologic Oncology
Street address 3855 Health Sciences Dr.
City La Jolla
State/province CA
ZIP/Postal code 92093
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM3693233 id81
GSM3693234 id82
GSM3693235 id83
This SubSeries is part of SuperSeries:
GSE129099 FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy
BioProject PRJNA530133
SRA SRP189981

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE129097_Id8ip_vs_Id8_DEG_all.txt.gz 805.7 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap