A novel microtubule inhibitor promotes tumor ferroptosis by attenuating SLC7A11/GPX4 signaling
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
MP-HJ-1b is a novel microtubule inhibitor that we designed and reported previously. Ferroptosis is a newly identified type of nonapoptotic cell death induced by ferrous catalysis and lipid peroxidation. Here, transcriptomics, proteomics, and molecular docking analyses were combined to explore the novel effects of MP-HJ-1b on tumors. Both omics analyses suggested that MP-HJ-1b affects ribosomes, and we confirmed that it inhibits the ribosomal component proteins RPL35 and MRPL28. Colchicine was used as an analog, and the results showed that MP-HJ-1b and colchicine increased reactive oxygen species and malondialdehyde levels and decreased reduced glutathione levels, suggesting that they promoted ferroptosis in HeLa cells. Specifically, MP-HJ-1b downregulated SLC7A11 and GPX4 to enhance the classical pathway of ferroptosis, while colchicine upregulated LC3A/B-II and enhanced autophagy. Clinically, the serum concentrations of ferrous ions, reduced glutathione, and Hcy were higher in cervical cancer patients than in healthy individuals. ALT, AST, Cho, HDL-C, and LDL-C levels were decreased in the serum of patients. Our study expands understanding of the way MP-HJ-1b promotes cell death and enriches research on microtubule inhibitors in the ferroptosis field.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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 it