 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 01, 2019 |
| Title |
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] |
| 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 KMF parental, KMF clone KT13 (FAK-/-), KT13 + GFP-FAK, KT13 + GFP-FAK R454, and KT13 + deltaGSK beta-catenin 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 |
| E-mail(s) |
dschlaepfer@ucsd.edu
|
| 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 (14)
|
|
| This SubSeries is part of SuperSeries: |
| GSE129099 |
FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy |
|
| Relations |
| BioProject |
PRJNA530132 |
| SRA |
SRP189982 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE129098_Group_key.txt.gz |
233 b |
(ftp)(http) |
TXT |
| GSE129098_fpkm_genename.txt.gz |
2.6 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...