RBFOX2 deregulation promotes pancreatic cancer progression and metastasis through alternative splicing
Bibliographic record
Abstract
ABSTRACT RNA splicing is an important biological process associated with cancer initiation and progression, yet in pancreatic cancer the role and regulation of splicing is not well understood. From a forward genetic screen in a mouse model of pancreatic cancer, we identified an enrichment of RNA binding proteins (RBPs) associated with the spliceosome. Here, we link deregulation of RBFOX2, an RBP of the FOX family, to pancreatic cancer progression and liver metastasis. We show that RBFOX2 regulation in pancreatic cancer occurs at both the RNA and protein level, and that nuclear localization of RBFOX2 is significantly reduced in poorly differentiated PDAC. Deregulation of RBFOX2 in PDAC is associated with an enrichment of exon exclusion events in transcripts encoding proteins involved in cytoskeletal remodeling and invadopodia programs that potentiate metastatic potential in vivo . Using splice-switching antisense oligonucleotides (AONs) and inducible cDNA isoforms, we demonstrate that RBFOX2 mediated exon exclusion in ABI1 controls the abundance and localization of ABI1 protein isoforms in pancreatic cancer cells, and that ABI1 splice-switching enhances cellular phenotypes associated with cancer cell stemness. Together, our data identify a novel role for RBFOX2 deregulation in promoting PDAC progression through alternative splicing regulation.
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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 | 0.000 |
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 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".