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| Status |
Public on Apr 07, 2021 |
| Title |
Cancer-associated exportin-6 upregulation inhibits the transcriptional repressive and anticancer effects of nuclear profilin-1 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Aberrant expression of nuclear transporters and altered subcellular localization of their cargo proteins are increasingly recognized as drivers and therapeutic targets of cancer. Here, we report that exportin-6, a nuclear exporter specific for actin/profilin-1, is upregulated in a broad range of cancers and associated with poor prognosis. Exportin-6 loss triggers antitumor effects in breast cancer cells in a profilin-1-dependent fashion. Nuclear profilin-1 interacts with the Super Elongation Complex (SEC), a positive transcriptional regulator of pro-cancer genes including MYC. Exportin-6 loss, by increasing nuclear profilin-1, inhibits SEC-dependent transcription and sensitizes breast cancer cells to inhibition of BET domain proteins. Thus, exportin-6 upregulation is a previously unrecognized cancer addiction that reduces the transcriptional inhibitory and anticancer activities of nuclear profilin-1.
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| Overall design |
Duplicate results of RNA-seq using breast cancer MCF-7 cell line stably expressing exportin-6 (wild type or RNAi-resistant) and infected with shRNAs targeting firefly luciferase or exportin-6.
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| Contributor(s) |
Shao J, Mooradian A |
| Citation(s) |
33596420 |
| Submission date |
Jan 28, 2020 |
| Last update date |
Apr 07, 2021 |
| Contact name |
Jieya Shao |
| Organization name |
Washington University in St. Louis
|
| Street address |
660 South Euclid Ave
|
| City |
Saint Louis |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA603508 |
| SRA |
SRP245599 |
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