Acharyya Swarnali, Guttridge Denis C
Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, Integrated Biomedical Graduate Program, The Arthur G. James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA.
Clin Cancer Res. 2007 Mar 1;13(5):1356-61. doi: 10.1158/1078-0432.CCR-06-2307.
Cachexia is a life-threatening consequence of cancer that diminishes both quality of life and survival. It is a syndrome that is characterized by extreme weight loss resulting mainly from the depletion of skeletal muscle. Research from the past decades investigating the mechanisms of tumor-induced muscle wasting has identified several key cachectic factors that act through the ubiquitin-dependent proteasome system. Signaling pathways that mediate the effects of these cachectic factors have also subsequently emerged. Here, we review some of these pathways specific to myostatin, nuclear factor kappaB, and the newly elucidated dystrophin glycoprotein complex. Although these molecules are likely to employ distinct modes of action, results suggest that they nevertheless maintain a link to the proteasome pathway. Therefore, although the proteasome remains a preferred choice for therapy, the continually emerging upstream signaling molecules serve as additional promising therapeutic targets for the treatment of tumor-induced muscle wasting.
恶病质是癌症的一种危及生命的后果，会降低生活质量并缩短生存期。它是一种以极度体重减轻为特征的综合征，主要源于骨骼肌的消耗。过去几十年对肿瘤诱导的肌肉萎缩机制的研究已经确定了几个关键的恶病质因子，它们通过泛素依赖性蛋白酶体系统发挥作用。随后也出现了介导这些恶病质因子作用的信号通路。在这里，我们回顾一些特定于肌肉生长抑制素、核因子κB以及新阐明的抗肌萎缩蛋白糖蛋白复合体的信号通路。尽管这些分子可能采用不同的作用方式，但结果表明它们与蛋白酶体途径仍存在联系。因此，尽管蛋白酶体仍然是治疗的首选，但不断出现的上游信号分子为治疗肿瘤诱导的肌肉萎缩提供了额外有前景的治疗靶点。
