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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 31, 2016 |
| Title |
Foxa2 and Cdx2 cooperate with Nkx2-1 to inhibit lung adenocarcinoma metastasis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Despite the fact that the majority of lung cancer deaths are due to metastasis, the molecular mechanisms driving metastat ic progression are poorly understood. Here, we present evidence that loss of Foxa2 and Cdx2 synergizes with loss of Nkx2- 1 to fully activate the metastatic program. These three lineage-specific transcription factors are consistently downregul ated in metastatic cells compared to non-metastatic cells. Knockdown of these three factors acts synergistically and is s ufficient to promote the metastatic potential of non-metastatic cells to that of naturally arising metastatic cells in vi vo. Furthermore, silencing of these three transcription factors is sufficient to account for a significant fraction of th e genes expression differences between the non-metastatic and metastatic states in lung adenocarcinoma, including upregul ated expression of the invadopodia component Tks5long, the embryonal proto-oncogene Hmga2, and the epithelial-to-mesenchy mal mediator Snail. Finally, analyses of tumors from a genetically-engineered mouse model and patients show that low expr ession of Nkx2-1, Foxa2, and Cdx2 strongly correlates with more advanced tumors and worse survival. Our findings reveal t hat a large part of the complex transcriptional network in metastasis can be controlled by a small number of regulatory n odes that function redundantly, and loss of multiple nodes is required to fully activate the metastatic program.
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| Overall design |
Cell lines derived from metastatic primrary tumor, and from non-metastatic primary tumors with and without subsequent knockdown of Nkx2-1, Foxa2 and Cdx2. All cell lines are in duplicate.
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| Contributor(s) |
Li CM, Gocheva V, Oudin MJ, Bhutkar A, Wang SY, Date SR, Ng SR, Whittaker CA, Bronson RT, Snyder EL, Gertler FB, Jacks T |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Aug 01, 2015 |
| 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) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA291647 |
| SRA |
SRP061916 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE71629_C_Li_RNAseq_2015_rsem_est_counts.xlsx |
1.4 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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