Functional Coupling of p38-Induced Up-regulation of BiP and Activation of RNA-Dependent Protein Kinase–Like Endoplasmic Reticulum Kinase to Drug Resistance of Dormant Carcinoma Cells
Bibliographic record
Abstract
It has been proposed that occult, disseminated metastatic cells are refractory to chemotherapy due to lack of proliferation. We have shown that p38 activation induces dormancy of squamous carcinoma cells. We now show that p38 signaling in these cells activates a prosurvival mechanism via the up-regulation of the endoplasmic reticulum (ER) chaperone BiP and increased activation of the ER stress-activated eukaryotic translation initiator factor 2alpha kinase RNA-dependent protein kinase-like ER kinase (PERK) allowing dormant tumor cells to resist drug toxicity. RNA interference and dominant-negative expression studies revealed that both BiP and PERK signaling promote survival and drug resistance of dormant cells, and that BiP up-regulation prevents Bax activation. We propose that stress-dependent activation of p38 via BiP up-regulation and PERK activation protects dormant tumor cells from stress insults, such as chemotherapy.
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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".