ArticleNature metabolism2025
Impaired cAMP-PKA-CREB1 signalling drives mitochondrial dysfunction in skeletal muscle during cancer cachexia.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Who cites it
5 citing papers in PubMed.
- Identification of immune and ferroptosis-related gene cysteine dioxygenase type 1 (CDO1) as a prognostic biomarker in colorectal cancer, relating to immunotherapy response distinction.World journal of surgical oncology · 2026Article
- C26 and CT26 colorectal cancer models exhibit divergent cachexia phenotypes, intramuscular inflammation, and protein turnover signaling.bioRxiv : the preprint server for biology · 2026Article
- Fiber-type vulnerability and proteostasis reprogramming in skeletal muscle during pancreatic cancer cachexia.JCI insight · 2026Article
- Immune signaling as a determinant of cellular identity and tissue function.Frontiers in immunology · 2026Review
- The role of exercise-induced myokines in cancer-associated inflammation and immune regulation: mechanisms and prospects.Frontiers in sports and active living · 2026Review
Corrections and comments
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Authors and funding
30 authors.
Funding
Abstract
Skeletal muscle wasting is a defining feature of cancer cachexia, a multifactorial syndrome that drastically compromises patient quality of life and treatment outcomes. Mitochondrial dysfunction is a major contributor to skeletal muscle wasting in cancer cachexia, yet the upstream molecular drivers remain elusive. Here we show that cancer impairs the activity of cAMP-dependent protein kinase A (PKA) and of its transcriptional effector CREB1 in skeletal muscle, ultimately contributing to the downregulation of a core transcriptional network that supports mitochondrial integrity and function. The restoration of cAMP-PKA-CREB1 signalling through pharmacological inhibition of the cAMP-hydrolysing phosphodiesterase 4 (PDE4) rescues the expression of mitochondrial-related genes, improves mitochondrial function and mitigates skeletal muscle wasting in male mice. Altogether, our data identify tumour-induced suppression of the cAMP-PKA-CREB1 axis as a central mechanism contributing to mitochondrial dysfunction in skeletal muscle during cancer cachexia. Furthermore, these findings highlight PDE4, particularly the PDE4D isoform, as a potential therapeutic target to preserve muscle mitochondrial function and counteract muscle wasting in cancer cachexia.
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Registered trials
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