F-BOX proteins in cancer cachexia and muscle wasting: Emerging regulators and therapeutic opportunities.
F-BOX proteins in cancer cachexia and muscle wasting: Emerging regulators and therapeutic opportunities.
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DOI：
10.1016/j.semcancer.2016.01.002
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发表时间：
2016-02
影响因子：
14.5
通讯作者：
Azmi AS
中科院分区：
文献类型：
--
作者：
Sukari A;Muqbil I;Mohammad RM;Philip PA;Azmi AS
癌症恶病质是一种衰弱的代谢综合征，其原因是疲劳、正常活动的障碍、与体重减轻相关的肌肉质量丧失，最终导致大多数晚期疾病患者死亡。经历骨骼肌萎缩的恶病质患者表现出SCF泛素连接酶(F-box)家族成员Atrogin-1(也称为MAFBx/FBXO32)的持续激活，同时肌肉环指蛋白1(MuRF1)也被激活。其他鲜为人知的F-box家族成员也正在成为支持肌肉萎缩途径的关键参与者。最近的工作强调了影响F-box家族成员的不同癌症信号机制的光谱，这些F-box家族成员在恶病质期间前馈肌肉萎缩相关基因。这些新的玩家提供了独特的机会，通过治疗靶向SCF蛋白连接酶来阻止恶病质引起的骨骼肌萎缩。相反，诱导蛋白质产生的策略可能有助于对抗这些F-box蛋白质的影响。通过这篇综述，我们提出了一些新的靶点，促进恶病质和肌肉萎缩中的阿托品-1信号转导，并强调了新的治疗机会，可以帮助更好地管理这种毁灭性和致命的疾病。
Cancer cachexia is a debilitating metabolic syndrome accounting for fatigue, an impairment of normal activities, loss of muscle mass associated with body weight loss eventually leading to death in majority of patients with advanced disease. Cachexia patients undergoing skeletal muscle atrophy show consistent activation of the SCF ubiquitin ligase (F-BOX) family member Atrogin-1 (also known as MAFBx/FBXO32) alongside the activation of the muscle ring finger protein1 (MuRF1). Other lesser known F-BOX family members are also emerging as key players supporting muscle wasting pathways. Recent work highlights a spectrum of different cancer signaling mechanisms impacting F-BOX family members that feed forward muscle atrophy related genes during cachexia. These novel players provide unique opportunities to block cachexia induced skeletal muscle atrophy by therapeutically targeting the SCF protein ligases. Conversely, strategies that induce the production of proteins may be helpful to counter the effects of these F-BOX proteins. Through this review, we bring forward some novel targets that promote atrogin-1 signaling in cachexia and muscle wasting and highlight newer therapeutic opportunities that can help in the better management of patients with this devastating and fatal disorder.