MCT4-driven CAF-mediated metabolic reprogramming in breast cancer microenvironment is a vulnerability targetable by miR-425-5p
Why this work is in the frame
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Bibliographic record
Abstract
Multiple oncogenic alterations contribute to breast cancer development. Metabolic reprogramming, deeply contributing to tumor microenvironment (TME) education, is now widely recognized as a hallmark of cancer. The reverse Warburg effect induces cancer-associated fibroblasts (CAFs) to produce and secrete L-lactate, enhancing malignant characteristics such as neoangiogenesis, metastatic dissemination, and treatment resistance. Monocarboxylate transporter (MCT) 4 is involved in lactate efflux from CAFs into stromal and epithelial cells. Here, we first assess the expression of miR-425-5p and its target MCT4 in breast cancer CAFs and normal fibroblasts. We analyzed the metabolic changes induced by miR-425-5p in CAFs and its role in the education of breast cancer epithelial cells. We show that miR-425-5p-induced MCT4 knockdown decreased lactate extrusion from CAFs and its availability in the TME. miR-425-5p overexpression induced profound metabolic transformation in CAFs, ultimately influencing breast cancer metabolism. Furthermore, miR-425-5p impaired the capacity of CAFs to sustain vessel formation and breast cancer cell migration, viability, and proliferation. These findings emphasize the key role of miR-425-5p in breast cancer metabolism and aggressiveness, and its possible importance for breast cancer therapy and monitoring.
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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) | 0.000 | 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 it