Abstract 4256: Characterization of the cellular inhibitor of apoptosis 1 (cIAP1) IRES trans-acting factors and their contribution to apoptotic resistance in rhabdomyosarcomas
Bibliographic record
Abstract
Abstract The cellular inhibitor of apoptosis protein 1 (cIAP1) is a key regulator of the NFκB signaling pathway and of caspase-8 mediated cell death in mammalian cells. cIAP1 expression is regulated at the translation level via an internal ribosome entry site (IRES). We have previously identified and characterized two IRES trans-acting factors - NF45 and IGF2BP1 - that bind specifically to the cIAP1 IRES and regulates its activity in the context of cell division and apoptosis. In this study, we characterized the minimal requirement of the cIAP1 IRES for these IRES trans-acting factors as well as other canonical translation factors. We also studied the contribution of cIAP1 expression regulation by these IRES trans-acting factors on the apoptotic resistance of rhabdomyosarcoma cancer cells. In particular, we show that the IRES trans-acting factor IGF2BP1 is overexpressed in a panel of rhabdomyosarcoma primary tumors and cell lines where it drives cIAP1 IRES-mediated translation, contributing to increased resistance to cell death. We also show that targeting cIAP1 by either IGF2BP1 knock-down or IAP antagonists delay RMS tumour growth in the presence of TNFα and improve survival in mice. Citation Format: Mame Daro Faye, Tyson E. Graber, Shawn Beug, Xiao Xiang, Benjamin Wild, Stephanie Langlois, Kyle N. Cowan, Robert G. Korneluk, Martin Holcik. Characterization of the cellular inhibitor of apoptosis 1 (cIAP1) IRES trans-acting factors and their contribution to apoptotic resistance in rhabdomyosarcomas. [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 4256. doi:10.1158/1538-7445.AM2014-4256
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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) | 0.002 | 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".