Abstract 476: The effects of the synthetic triterpenoid acetylenic tricyclic bis-(cyano enone) on cell migration and epithelial-to-mesenchymal transition
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Abstract During metastasis, epithelial tumor cells undergo epithelial to mesenchymal transition (EMT) allowing them to migrate to distant organs to establish secondary tumors. Cell migration is initiated by the asymmetrical localization of polarity proteins towards the leading edge. This stimulates the reorganization and polymerization of the microtubule and actin cytoskeletons, which form protrusions in the plasma membrane to drive the cell forwards. Metastasis accounts for over 90% of cancer related deaths, thus a reduction in cancer mortality will require therapies aimed at preventing or delaying the events of metastasis. Our lab has identified the synthetic triterpenoid, CDDO-Im, as a potent inhibitor of cell migration by inhibiting the polymerization of branched actin and disrupting the organization of the microtubule network (To et al., J Biol Chem. 2008, 2010). Recently, TBE-31 has been developed, which is a smaller 3-ring compound that contains the same active functional groups as CDDO-Im. Here we assessed the effects of TBE-31 on cell migration and EMT. TBE-31 was found to displace the polarity proteins from the leading edge of migrating cells and induce multiple cell protrusions. The microtubule network was also observed to be disorganized and the rate of polymerization for both tubulin and actin were lowered in the presence of TBE-31. These effects are believed to allow submicromolar concentrations TBE-31 to inhibit cell migration by as much as 60%. Finally, the reorganization of actin and formation of stress fibers normally associated with EMT was also inhibited by TBE-31 in A549 tumor cells. We are now confirming our results in a panel of lung tumor cell lines. In conclusion, TBE-31 disrupts the cytoskeleton and inhibits cell migration and preliminary data suggest TBE-31 may also hinder EMT. Further research will be needed to determine the overall impact these effects have on the progression of metastasis. 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 476. doi:1538-7445.AM2012-476
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 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 it