Abstract 292: Breast cancer malignancy is regulated by PAX5 through the disruption of FAK1 signaling.
Bibliographic record
Abstract
Abstract Breast cancer is the most common cancer diagnosed in women worldwide. 30% of these women will succumb to their disease. More specifically, metastasis accounts for 90% of deaths in breast cancers patients. Therefore, the study of genetic factors regulating cancer malignancy is a top priority to mitigate the morbidity and mortality associated to this disease. PAX5 (Paired Box 5) is a transcriptional factor normally implicated in embryogenesis and B cell differentiation. However, the aberrant expression of PAX5 is associated to several types of cancer pathology and more recently in breast cancer. We have recently reported that PAX5 promotes epithelialisation and its expression inversely correlates with the Focal Adhesion Kinase 1 (FAK1), a key component in cancer motility and invasion leading to metastasis. On one hand, these finding suggest that PAX5 could attenuate FAK-mediated epithelial-mesenchymal transitioning (EMT) of primary tumors. On the other hand, PAX5 could also initiate the mesenchymal-epithelial transitioning (MET) of circulating cancer cells enabling them to colonize and establish secondary tumours. In this study we set out to validate the role of PAX5 in the metastatic cascade of mammary tumours, particularly to uncover the molecular regulation of FAK1 cascades through PAX5 in breast cancer cell malignancy. Through conditional expression of the PAX5 gene in breast cancer cells, we demonstrate experimentally a negative regulation of FAK1 protein and phosphorylation levels mediated by PAX5 over expression. We also confirm that PAX5 suppresses the transcriptional expression of FAK1. Further investigation shows a PAX5-mediated suppression of FAK1 signaling pathways (e.i. AKT, p38, JNK and Paxillin) leading to attenuated cancer cell proliferation, death and migration processes. These findings bring light to molecular mechanisms driving breast cancer malignancy and benefit our quest in the development of diagnostic and therapeutic strategies. Citation Format: Sami Benzina, Pierre O'Brien, Roxann Guerrette, Gilles Robichaud. Breast cancer malignancy is regulated by PAX5 through the disruption of FAK1 signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 292. doi:10.1158/1538-7445.AM2013-292
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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 | 0.000 |
| 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) | 0.004 | 0.001 |
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".