Regulation of Breast Cancer Progression by Phosphorylation of the Tumor Suppressor Tropomyosin-1 Alpha
Bibliographic record
Abstract
Background: Tropomyosin 1 alpha chain (Tm1) is an actin-binding protein that regulates the endothelial cell response to oxidative stress following its phosphorylation at Serine 283 (S283). Tm1 is also a major tumor suppressor in breast cancer. In the present study, we investigated the role of phosphorylation of Tm1 in regulating its tumor suppressor properties. Methods: MDA MB231 breast cancer cells stably overexpressing wild type form of Tm1 or Tm1 mutants (S283A and S283E) were generated. Proliferation and cell viability were assayed by means of the enzymatic cleavage of the tetrazolium salt WST-1 to formazan dye by cellular mitochondrial dehydrogenases. Adhesion assays were performed at various periods of time on cells grown on plastic. Cell migration was evaluated by using the wound-healing assay and by measuring transendothelial migration of cancer cells. Malignant transformation in vitro was determined by using the anchorage-independent growth assay on soft agar. Results: We found that cells expressing the phosphomimetic form of Tm1 S283E/Tm1 are characterized by an increased adhesion to the substratum. Moreover, the migration of MDA-MB231/S283E/Tm1 cells in a wound closure assay is reduced compared to parental cells or those expressing the non-phosphorylatable form of Tm1 (S283A). Similarly, the transendothelial migration of MDA-MB231/S283E/Tm1 cells is also reduced as compared to the other cell lines. Moreover, we found that the cells expressing the S283A mutants form more colonies in soft agar that those expressing the S283E mutants. Conclusion: Phosphorylation of Tm1 at Ser283 contributes to its anti-tumor properties, and this effect results mainly from an increase in cell adhesion associated with a decrease in their migratory and invasive potentials.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".