Abstract P5-11-08: SRA/SRAP contributes to TGF-b1 induced cell motility in cancer cells
Bibliographic record
Abstract
Abstract The steroid receptor RNA activator gene (SRA1) is a particularly intriguing genetic system in that both the corresponding RNA (SRA) and protein (SRAP) have been proven to be functional. Accumulated evidence overall suggests that both molecules act as distinct co-regulators of transcription, housed in ribonucleo-protein complexes able to positively or negatively regulate the activity of multiple transcription factors including -but not limited to- several nuclear receptors, MyoD and DAX-1. A role for SRA/SRAP deregulation during breast tumorigenesis has been suggested. Indeed, not only do these molecules regulate the activity of both Estrogen Receptors, these major players in breast cancer etiology, but it has also been shown that SRA RNA is more highly expressed in breast tumors than in normal tissue, and that high levels of SRAP correlated to poorer survival in specific subsets of breast cancer patients. In order to identify the genes and pathways regulated by SRA/SRAP, we performed deep sequencing of transcriptomes from MDA-MB-231 cells depleted of these molecules following RNA interference. The expression of 149 genes was consistently and significantly altered in four independent experiments comparing control RNAi vs SRA RNAi. Interestingly, cluster analysis using Ingenuity software defined a subset of genes (23 out of 149) directly associated with cell movement. Among them figured TGFBR1 (ALK5), a cell surface receptor-kinase mediating TGF-b signalling and a known promoter of cell motility in breast cancer cells. We have now confirmed by quantitative PCR analysis a 40% decrease, upon SRA/SRAP depletion, of TGFBR1 mRNA expression in MDA-MB-231 cells as well as in other breast (MCF7, T5) and non-breast (Hela) cancer cell lines. Consistent with this decrease a drop to 60% of the basal TGFBR1 protein expression is seen by Western blot when MDA-MB-231 cells are depleted of SRA/SRAP. Western blot analyses also revealed that phosphorylation of several SMAD molecules, downstream effectors of TGFBR1 activation by TGF-β1, is impaired in the absence of SRA/SRAP in both MDA-MB-231 and Hela cells. This suggests that SRA/SRAP could potentially regulate TGF beta induced cell motility. Using migration cell assays, we have now confirmed that upon TGF-β1 treatment for 6 hours, SRA/SRAP depleted cells had a significant decrease in migration as compared to control cells. Accordingly, live cell migration assays generated by a time-lapse videomicroscopy system, showed an increased track length and speed in both Hela and 231 cells over-expressed SRAP upon 10 h TGF-β1 treatment. Taken together, these data suggest a cross-talk between SRA/SRAP and TGF-β signalling and induced cell motility. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-11-08.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 0.005 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".