Cancer and Chemotherapy Contribute to Muscle Loss by Activating Common Signaling Pathways

Area of Science:

• Proteomics
• Molecular Biology
• Oncology

Background:

• Cachexia, a complication of colorectal cancer, involves muscle and fat depletion.
• Chemotherapy, such as Folfiri, can exacerbate cachexia-related symptoms.

Purpose of the Study:

• To investigate the proteomic signature of cachexia in Colon-26 (C26) tumor-bearing mice and Folfiri-treated mice.
• To identify common and distinct molecular changes associated with cancer- and chemotherapy-induced muscle wasting.

Main Methods:

• Quantitative LC-MS/MS proteomics was employed to analyze quadriceps muscle proteomes.
• Differential protein expression analysis and pathway analysis were performed.

Main Results:

• Significant changes in 386 proteins (Folfiri) and 269 proteins (C26) were identified.
• 240 proteins were commonly modulated, with 218 down-regulated in both conditions, primarily metabolic and structural proteins.
• Mitochondrial dysfunction, altered oxidative phosphorylation, and impaired fatty acid metabolism were observed in both models.

Conclusions:

• Both colorectal cancer and chemotherapy activate common pathways contributing to muscle loss.
• Distinct inflammatory and metabolic profiles were noted between C26 and Folfiri-induced cachexia.
• Combined therapeutic strategies targeting tumor growth and chemotherapy side effects are warranted.