Abstract 2883: Vimentin downregulation modulates p53 levels and apoptosis in cancer cells
Bibliographic record
Abstract
Abstract Vimentin, a mesenchymal-specific intermediate filament (IF) protein, is often express in epithelial cancers exhibiting a de-differentiated phenotype. Vimentin is associated with increased chemoresistance and metastatic potential. Chemoresistance is a multifactorial phenomenon which is a major cause of treatment failure in human cancer. Some IF proteins are known to promote resistance to stress-induced apoptosis, but the role of vimentin in this process is still unknown. In the present study, we investigate the role of vimentin in response to apoptosis-induced chemotherapeutic drugs in different epithelial carcinoma cell lines. Surprisingly, using siRNA, our results show that vimentin downregulation decreases caspase-3 and PARP cleavage induced by cisplatin, doxorubicin and TNFalpha. This unexpected result could be explained by the decrease of p53 protein levels in vimentin-downregulated cells. Indeed, we observed that vimentin knockdown decreases p53 levels in a proteasome-dependent manner and also modulates p53 ubiquitination. PI3K/Akt pathway is well known to promote chemoresistant phenotype in different cancers and Akt can also regulate p53 function. Our results show that vimentin-induced p53 decrease is associated with an increase of Akt phosphorylation. We propose that vimentin knockdown results in an increase of Akt activity which in turn regulates ubiquitination and proteasomal degradation of p53. We have recently showed that Akt isoforms regulates vimentin and keratins IF expression in epithelial cancer cells, suggesting that IF proteins are directly involved in PI3K/Akt signaling pathway. To our knowledge, these results represent the first indication that vimentin could regulate Akt activity and p53 levels in response to apoptosis-induced chemotherapeutic drugs. These results support the hypothesis that modulation of IF expression plays an active role in cancer progression and that vimentin could be a possible target for cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2883. doi:10.1158/1538-7445.AM2011-2883
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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) | 0.003 | 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".