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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 18, 2018 |
| Title |
GKAP acts as a genetic modulator of NMDAR signaling to govern tumor invasiveness |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Genetic linkage analysis suggested that GKAP, a scaffold protein of the NMDA receptor (NMDAR), was a potential modifier of invasion in a mouse model of pancreatic neuroendocrine cancer (PanNET). Here we establish that GKAP governs invasive growth and treatment response of PanNET via its pivotal role in regulating the NMDAR pathway activity. Combining genetic knockdown of GKAP and pharmacological inhibition of NMDAR, we distilled gene expression signatures orchestrated by the NMDAR-GKAP axis, in addition to identifying two downstream effectors FMRP and HSF-1. Additionally, GKAP, FMRP, and HSF1 are functionally implicated in invasiveness of pancreatic ductal adenocarcinoma. Finally, gene expression signatures in tumors with low NMDAR activity are significantly associated with favorable patient prognosis in several cancer types.
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| Overall design |
mPanNET tumors from different strain backgrounds: C57Bl/6 (B6) and C3HeB/Fe (C3H). Within B6 tumors, either treated with a potent NMDAR antagonist MK801 or untreated/saline-treated controls.
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| Contributor(s) |
Li L, Zeng Q, Bhutkar A, Galván J, Karamitopoulou E, Necsulea A, Noordermeer D, Piersigilli A, Peng M, Perren A, Zlobec I, Robinson H, Iruela-Arispe ML, Hanahan D |
| Citation(s) |
29606348 |
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| Submission date |
Aug 13, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
A Bhutkar |
| Organization name |
MIT
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| Street address |
77 Massachusetts Avenue
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02139 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA398161 |
| SRA |
SRP115363 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE102598_LL_RNAseq_2017_normalized_counts_mm9.xlsx.gz |
4.5 Mb |
(ftp)(http) |
XLSX |
| GSE102598_LL_RNAseq_2017_rsem_est_counts_mm9.xlsx.gz |
2.5 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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