Abstract 1121: Extracellular matrix-integrin B1 signaling is a major mediator of epithelial-to-mesenchymal transition and contributes to prostate cancer invasion and metastasis
Bibliographic record
Abstract
Abstract Within North America, prostate cancer is the most commonly diagnosed cancer in men with devastating implications deriving from metastasis, particularly those established in the bone. We have elucidated mechanisms by which prostate cancer undergoes metastasis with particular focus on the relationship between extracellular-matrix binding proteins, Integrin B1 (ITGB1) and epithelial-to-mesenchymal transition (EMT). Previous results in the laboratory suggested that prostate tumor cells depleted of ITGB1 were unable to form colonies in soft agarose and were impaired in their invasive abilities in vitro. In order to determine the possible mechanisms by which ITGB1 controlled these phenotypes, we performed numerous genetic techniques including siRNA targeted depletion of ITGB1 and subsequent profiling of pathway specific message RNA by RTqPCR to monitor the effects ITGB1 depletion on factors known to control EMT which is also associated with cell invasion. We found that prostate tumor cells depleted of ITGB1 had altered expression of numerous genes associated with EMT or cell invasion, many of which have been validated by RT-qPCR and western blot. In particular, a protease inhibitor SERPINE1 also known as Plasminogen Activator Inhibitor 1 (PAI-1) which is associated with EMT has been established as a target of ITGB1 regulation, in part via the ability of ITGB1 to regulate upstream factors associated with SERPINE1 expression such as TGFB2. Of particular interest to prostate cancer bone metastasis, we further found that collagen I interacting with ITGB1 significantly upregulated this pathway, and given the known role of EMT in mediating resistance to anti-cancer agents, this finding could help elucidate novel targets for the development of new drugs to treat prostate cancer bone metastasis. Citation Format: Steven R. Bugiel, Elisabeth McKittrick, Huijun Zhao, Grant A. Howe, Christina L. Addison. Extracellular matrix-integrin B1 signaling is a major mediator of epithelial-to-mesenchymal transition and contributes to prostate cancer invasion and metastasis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1121. doi:10.1158/1538-7445.AM2014-1121
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".