The Mitogen-Activated Protein Kinase Kinase 4 Has a Pro-Oncogenic Role in Skin Cancer
Bibliographic record
Abstract
The mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) is a nonredundant component of stress-activated MAPK signaling modules. Its function in tumorigenesis remains highly controversial with some studies indicating that MKK4 is a tumor suppressor, whereas others have reported a pro-oncogenic role. To clarify the role of MKK4 in cancer, we have created a novel mouse model to test the effect of the specific loss of MKK4 in the epidermis on the formation of papillomas caused by activated ras mutation. We have discovered that skin-specific MKK4-deficient mice are resistant to carcinogen-induced tumorigenesis. One mechanism by which MKK4 promotes cell proliferation and the formation of tumors is by increasing epidermal growth factor receptor expression through the c-Jun NH(2)-terminal protein kinase/c-Jun signaling pathway. Together, our results provide the first genetic demonstration that MKK4 is essential to mediate the oncogenic effect of Ras in vivo, thereby validating MKK4 as a potential drug target for cancer therapy.
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.
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 | 0.001 |
| 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".