Combinational therapy targeting the MET‐mTOR‐ROS loop disrupts mitochondrial autoregulatory machinery of liver cancer
Why this work is in the frame
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Bibliographic record
Abstract
A wide variety of regulators have been identified in mechanistic target of rapamycin (mTOR) activation; however, the protective mechanisms of mTOR inactivation are still largely unknown, especially in tumor growth. Here, we have found the hepatocyte growth factor (HGF) receptor (MET) is required for mTOR activation-stimulated mitochondrial oxidative phosphorylation (OXPHOS) in a phosphorylation-dependent manner in liver cancer. Intriguingly, we observed mitochondrial quality dictates the regulatory effects of MET on mTOR and OXPHOS. Once overloaded, mitochondrial reactive oxygen species (ROS) inhibits mTOR activity and OXPHOS performance to prevent mitochondrial dysfunction-induced tumor cell death, by disrupting MET dimerization to block its autophosphorylation and interaction with vacuolar ATP synthase (V-ATPase). The MET-mTOR-ROS loop acts as a protective checkpoint in liver cancer, and thus this autoregulatory machinery is a promising combinational target for liver cancer therapy.
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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 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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 it