Tumor‑muscle communication in cancer‑associated cachexia (Review)

Cancer progression is characterized by the ability of cancer cells to grow uncontrollably, invade adjacent tissues and eventually metastasize, which is typically accompanied by systemic effects. Cachexia, a catabolic state characterized by the loss of skeletal muscle mass and anorexia, is thought to result from the release of inflammatory molecules and other mediators from the tumor niche. The loss of skeletal muscle mass that characterizes cachexia is due to an exacerbation of proteolysis in muscle cells, a catabolic process that is dependent on inflammatory factors and extracellular vesicles (EVs) released by tumor cells. EVs activate various cellular signaling pathways that result in the nuclear translocation of NF-κB. These EVs carry various cargoes, including interleukins, microRNAs and receptors for advanced glycation end-products. When reaching muscle cells, these factors lead to an energy imbalance, increased oxidative stress, and the transcription of ubiquitin ligases such as muscle RING finger 1 and muscle atrophy F-box (Atrogin-1). While EVs appear to play an important role in cachexia, more evidence is needed to determine the interaction of the different cellular signaling pathways involved in the communication between the tumor cells and skeletal muscle cells, as well as to characterize the EVs derived from tumor cells and understand how they may contribute to the varying severity levels of cachexia syndrome. In cachexia, muscle wasting is driven by pro-inflammatory and catabolic factors released by tumor cells, leading to a negative energy balance. These factors activate the ubiquitin-proteasome pathway and suppress the PI3K/AKT/mTOR pathway. This line of research may lead to the development of new therapeutic strategies aimed at improving survival in patients with cancer with cachexia.