NLRX1 Acts as an Epithelial-Intrinsic Tumor Suppressor through the Modulation of TNF-Mediated Proliferation
Bibliographic record
Abstract
The mitochondrial Nod-like receptor protein NLRX1 protects against colorectal tumorigenesis through mechanisms that remain unclear. Using mice with an intestinal epithelial cells (IEC)-specific deletion of Nlrx1, we find that NLRX1 provides an IEC-intrinsic protection against colitis-associated carcinogenesis in the colon. These Nlrx1 mutant mice have increased expression of Tnf, Egf, and Tgfb1, three factors essential for wound healing, as well as increased epithelial proliferation during the epithelial regeneration phase following injury triggered by dextran sodium sulfate. In primary intestinal organoids lacking Nlrx1, stimulation with TNF resulted in exacerbated proliferation and expression of the intestinal stem cell markers Olfm4 and Myb. This hyper-proliferation response was associated with increased activation of Akt and NF-κB pathways in response to TNF stimulation. Together, these results identify NLRX1 as a suppressor of colonic tumorigenesis that acts by controlling epithelial proliferation in the intestine during the regeneration phase following mucosal injury.
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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 | 0.000 | 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) | 0.000 | 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".