Abstract B31: The RhoGEF GEF-H1 is required for RAS oncogene-driven pancreatic cancer
Bibliographic record
Abstract
Abstract Cellular transformation by oncogenic RAS engages the MAPK pathway under strict spatiotemporal regulation by the scaffold protein KSR-1. Here, we find using a whole genome functional shRNA-based screen, that the guanine nucleotide exchange factor GEF-H1 plays a critical role in a positive feedback loop for the RAS/MAPK pathway independently of its RhoGEF activity. GEF-H1 acts as an adaptor protein, linking the PP2A B' subunits to KSR-1, required for the dephosphorylation of KSR-1 S392 and activation of MAPK signaling. GEF-H1 is required for the growth and survival of RASV12-transformed cells and pancreatic xenografts. GEF-H1 expression is induced by oncogenic RAS and is correlated with pancreatic neoplastic progression. Our results therefore identify GEF-H1 as an amplifier of MAPK signaling required for cell transformation and provide mechanistic insight into the progression of RAS-mutant tumors. Citation Format: Jane Cullis, Dedi Meiri, Maria Jose-Sandi, Oliver Kent, Mauricio Medrano, Daphna Mokady, Ming Tsao, Anne-Claude Gingras, Robert Rottapel. The RhoGEF GEF-H1 is required for RAS oncogene-driven pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B31. doi: 10.1158/1557-3125.RASONC14-B31
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How this classification was reachedexpand
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 | 0.001 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".