The Role of Skeletal Muscle Mitochondria in Colorectal Cancer Related Cachexia: Friends or Foes?
Britt van de HaterdKenneth VerbovenFrank VandenabeeleAnouk AgtenPublished in: International journal of molecular sciences (2022)
Up to 60% of colorectal cancer (CRC) patients develop cachexia. The presence of CRC related cachexia is associated with more adverse events during systemic therapy, leading to a high mortality rate. The main manifestation in CRC related cachexia is the loss of skeletal muscle mass, resulting from an imbalance between skeletal muscle protein synthesis and protein degradation. In CRC related cachexia, systemic inflammation, oxidative stress, and proteolytic systems lead to mitochondrial dysfunction, resulting in an imbalanced skeletal muscle metabolism. Mitochondria fulfill an important function in muscle maintenance. Thus, preservation of the skeletal muscle mitochondrial homeostasis may contribute to prevent the loss of muscle mass. However, it remains elusive whether mitochondria play a benign or malignant role in the development of cancer cachexia. This review summarizes current (mostly preclinical) evidence about the role of skeletal muscle mitochondria in the development of CRC related cachexia. Future human research is necessary to determine the physiological role of skeletal muscle mitochondria in the development of human CRC related cachexia.
Keyphrases
- skeletal muscle
- insulin resistance
- oxidative stress
- endothelial cells
- end stage renal disease
- stem cells
- adipose tissue
- chronic kidney disease
- metabolic syndrome
- cardiovascular disease
- signaling pathway
- squamous cell carcinoma
- dna damage
- coronary artery disease
- risk factors
- ischemia reperfusion injury
- heat stress
- papillary thyroid
- protein protein
- binding protein