5-Fluorouracil-based chemotherapy disrupts autophagy flux and protein synthesis in cultured myotubes: a role for mTORC1 signaling
What this study shows
FOLFOX and oxaliplatin disrupted mTORC1/AMPK regulation of autophagy flux and protein synthesis in cultured myotubes; the effect was not easily reversible on drug withdrawal. Rapamycin (but not metformin) restored autophagy flux and AMPK phosphorylation, though without restoring protein synthesis.
Abstract
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5-Fluorouracil-based chemotherapies, such as FOLFOX (5-fluorouracil, leucovorin, oxaliplatin), are used to treat colon cancer but also induce skeletal muscle toxicities. While FOLFOX can disrupt muscle autophagy signaling in vivo, the upstream mechanisms underlying this effect, as well as the roles of mTORC1 and AMPK signaling, require further investigation.
Read the full abstract on PubMed →At a glance
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| Evidence type | M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: C2C12 mouse myotubes (in vitro), with and without CT26 colon-tumor-cell-conditioned media) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is. |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | C2C12 mouse myotubes (in vitro), with and without CT26 colon-tumor-cell-conditioned media |
| Journal | American Journal of Physiology-Cell Physiology |
| Year | 2026 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1152/ajpcell.00321.2026 · PMID 42734427 |
Where this study fits
How this study connects to the pathway map, open questions, people and other studies in the Atlas.
People in the Atlas
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Muscle-biology researcher studying how cancer, chemotherapy and cachexia disrupt skeletal-muscle protein turnover and autophagy
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Muscle physiologist studying cancer-associated cachexia and how chemotherapy and exercise remodel skeletal-muscle metabolism
More: 2 other authors
No profile yet: Zhang Q, Jenkins T
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Topics
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | 5-FU, 5-FU+leucovorin, oxaliplatin, combined FOLFOX regimen; rescue with rapamycin or metformin |
| Target | mTORC1/AMPK/ULK1 signaling and autophagy flux |
| Model | Mouse (C2C12 myotubes, in vitro) |
| Effect | FOLFOX/oxaliplatin suppressed autophagy flux, AMPK and ULK1(S555) phosphorylation, and protein synthesis; effect persisted after drug withdrawal; rapamycin (not metformin) restored autophagy flux and AMPK phosphorylation without restoring protein synthesis |
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