Abstract 3254: Cadherin-11 function is required for full neoplastic transformation by v-Src
Bibliographic record
Abstract
Abstract The signal transducer and activator of transcription-3 (Stat3) has emerged as an important signal transducer with a role in cancer etiology. Following activation of a number of growth factor or cytokine receptors or expression of oncogenes such as vSrc, Stat3 is phosphorylated at tyr-705, dimerizes and migrates to the nucleus where it activates transcription from a number of genes involved in cell division and survival. We recently discovered a novel pathway of activation of Stat3, triggered by cadherin engagement. Stat3 activation was caused by a striking upregulation of the Rac GTPase and IL6, and induced downregulation of the p53 antioncogene, upregulation of anti-apoptotic genes and a potent survival signal. A large number of oncogenes such as vSrc activate the E2F transcription factor, found to be hyperactive in many cancers. E2F induces the expression of genes involved in cell division, as well as a number of receptor tyrosine kinases, that can, in turn, activate Stat3. However, at the same time E2F is a potent apoptosis inducer, hence the high demand of transformed cells for survival signals. Since cadherin engagement activates Stat3, a potent survival signal, we examined the effect of downregulation of cadherin-11 upon transformation of mouse Balb/c3T3 fibroblasts by vSrc. Cadherin-11 knockdown through shRNA expression with a retroviral vector caused a dramatic reduction in Stat3 activity. At the same time, expression of vSrc in cadherin-11 knockdown cells failed to cause transformation; in the contrary, vSrc expression induced apoptosis. These data indicate that cadherin-11 is necessary for full neoplastic transformation of mouse fibroblasts by vSrc. This is especially remarkable because Src has been shown to have a negative effect upon, although not eliminate cadherin function, since Stat3 activity was, in fact increased in vSrc-expressing cells upon cadherin engagement. Therefore, it appears that the residual amounts of cadherin-11 present are sufficient to activate Stat3 and prevent apoptosis induced by the Src/E2F axis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3254. doi:1538-7445.AM2012-3254
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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) | 0.005 | 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".