|
|
|
| Muscle protein breakdown in cancer cachexia#br# |
| Zhang Ying1, Wang Xinying2 |
| 1.Department of Cardiothoracic Surgery, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu, China；2.Department of General Surgery, General Hospital of Eastern Theater Command, Nanjing 210002, Jiangsu, China |
|
|
|
|
Abstract Muscle wasting is the central characteristic of cancer cachexia, which is associated with increased postoperative complication rates, increased susceptibility to chemotherapy toxicity, and decreased chance of survival. The muscle loss is caused by an imbalance between protein synthesis and degradation. In cancer patients, increased muscle protein breakdown seemed to play a more important role than decreased protein synthesis. The ubiquitin proteasome system (UPS) and autophagy lysosome system (ALS) are major intracellular proteolytic systems. UPS is the primary proteolytic route for short-lived, misfolded, and damaged proteins. It has important functions in the regulation of cell signaling and transcription and is involved in a variety of cellular functions, including cell cycle progression, cell survival, proliferation, apoptosis, and other critical cellular pathways. ALP recognizes and removes large and potentially dangerous cellular components such as protein aggregates and dysfunctional or superfluous organelles and has emerged as a crucial adaptive mechanism to cope with various cellular stresses. In the past, ubiquitin and the autophagy system were considered to be two independent systems. However, more and more studies show that they are closely related and functionally related systems,which serve complimentary roles in degrading cellular constituents and might be coordinately activated by common signaling mechanisms. In this review we will describe the involvement of the ubiquitin proteasome and autophagy lysosome systems in cancer cachexia that regulate tumor-induced protein breakdown in muscle.
|
|
|
|
|
|
1.LEVOLGER S, VAN VUGT J L, DE BRUIN R W, et al. Systematic review of sarcopenia in patients operated on for gastrointestinal and hepatopancreatobiliary malignancies［J］. Br J Surg, 2015, 102(12):1448-1458.
2.ZHANG Y, WANG J P, WANG X L, et al. Computed tomography-quantified body composition predicts short-term outcomes after gastrectomy in gastric cancer［J］. Curr Oncol, 2018, 25(5):e411-e422.
3.VEGA M C, LAVIANO A, PIMENTEL G D. Sarcopenia and chemotherapy-mediated toxicity［J］. Einstein (Sao Paulo), 2016, 14(4):580-584.
4.NAKAMURA R, INAGE Y, TOBITA R. Sarcopenia in resected NSCLC: effect on postoperative outcomes［J］. J Thorac Oncol.2018, 13(7):895-903.
5.MACDONALD A J, JOHNS N, STEPHENS N, et al. Habitual myofibrillar protein synthesis is normal in patients with upper gi cancer cachexia［J］. Clin Cancer Res, 2015, 21(7):1734-1740.
6.BILODEAU P A, WING S S. The ubiquitin proteasome system in atrophying skeletal muscle: roles and regulation［J］. Am J Physiol Cell Physiol, 2016, 311(3):C392-C403.
7.ANTONIOU N, LAGOPATI N, BALOURDAS D I, et al. The role of E3, E4 ubiquitin ligase (ube4b) in human pathologies［J］. Cancers (Basel), 2019, 12(1):62
8.ROM O, REZNICK A Z. The role of E3 ubiquitin-ligases MuRF-1 and MAFbx in loss of skeletal muscle mass［J］. Free Radic Biol Med, 2016, 98:218-230.
9.TARDIF N, KLAUDE M, LUNDELL L, et al. Autophagic-lysosomal pathway is the main proteolytic system modified in the skeletal muscle of esophageal cancer patients［J］. Am J Clin Nutr, 2013, 98(6):1485-1492.
10.ANIORT J, STELLA A, PHILIPPONNET C, et al. Muscle wasting in patients with end-stage renal disease or early-stage lung cancer: common mechanisms at work［J］. J Am Med Dir Assoc, 2019, 10(2):323-337.
11.ADAMS V, BOWEN T S, WERNER S, et al. Small-molecule-mediated chemical knock-down of MuRF1/MuRF2 and attenuation of diaphragm dysfunction in chronic heart failure［J］. J Cachexia Sarcopenia Muscle, 2019, 10(5):1102-1115.
12.BEDARD N, JAMMOUL S, MOORE T, et al. Inactivation of the ubiquitin-specific protease 19 deubiquitinating enzymeprotects against muscle wasting［J］. FASEB J, 2015, 29:3889-3898.
13.YANG Y, KLIONSKY D J. Autophagy and disease: Unanswered questions［J］. Cell Death Differ, 2020, 27(3):858-871.
14.AVERSA Z, PIN F, LUCIA S, et al. Autophagy is induced in the skeletal muscle of cachectic cancer patients［J］. Sci Rep, 2016, 6:30340.
15.PUIG-VILANOVA E, Rodriguez D A, LLORETA J, et al. Oxidative stress, redox signaling pathways, and autophagyin cachectic muscles of male patients with advanced COPD and lung cancer［J］. Free Radic Biol Med, 2015, 79:91-108.
16.KARSLI-UZUNBAS G, GUO JY, PRICE S, et al. Autophagy is required for glucose homeostasis and lung tumormaintenance［J］. Cancer Discov, 2014, 4:914-927.
17.GARCIA-PRAT L, MARTINEZ-VICENTE M, PERDIGUERO E, et al. Autophagy maintains stemness by preventing senescence［J］. Nature, 2016, 529(7584):37-42.
18.RANJBAR K, BALLARO R, BOVER Q, et al. Combined exercise training positively affects muscle wasting in tumor-bearing mice［J］. Med Sci Sports Exerc, 2019, 51(7):1387-1395.
19.DIKIC I. Proteasomal and autophagic degradation systems［J］. Annu Rev Biochem, 2017, 86:193-224.
20.ZHANG Y, WANG J, WANG X, et al. The autophagic-lysosomal and ubiquitin proteasome systems are simultaneously activated in the skeletal muscle of gastric cancer patients with cachexia［J］. Am J Clin Nutr, 2020, 111(3):570-579. |
|
|
|
