Cancer cachexia is a complex metabolic disease so far lacking effective therapy, and it accounts for approximately one third of all cancer-related deaths worldwide. The extracellular ligand Wnt7a has a dual function in skeletal muscle, inducing the anabolic AKT/mammalian target of rapamycin (mTOR) pathway in myofibers and driving muscle stem cell expansion in skeletal muscle, making it a promising candidate for treatment of muscle wasting diseases. In murine and human myotubes, Wnt7a activates the anabolic AKT/mTOR pathway, thereby preventing cachexia-induced atrophy with a single application being sufficient to prevent atrophy independently of the tumor cell type causing cachexia. Addition of Wnt7a also improved activation and differentiation of muscle stem cells in cancer cachexia, a condition under which skeletal muscle regeneration is severely impaired due to stalled muscle stem cell differentiation. Finally, we show that Wnt7a prevents cancer cachexia in an in vivo mouse model based on C26 colon carcinoma cells. Wnt7a has a dual role in cachectic skeletal muscle; that is, it effectively counteracts muscle wasting through activation of the anabolic AKT/mTOR pathway and, furthermore, reverts the loss of muscle stem cell functionality due to cancer cachexia, making Wnt7a a promising candidate for an ameliorative treatment of cancer cachexia.

癌症恶病质是迄今为止尚无有效疗法的复杂代谢性疾病，约占全世界所有癌症相关死亡的三分之一。细胞外配体Wnt7a在骨骼肌中具有双重功能，诱导肌纤维中合成代谢的AKT /哺乳动物雷帕霉素（mTOR）途径靶标并驱动骨骼肌中的肌肉干细胞扩增，使其成为治疗肌肉萎缩疾病的有希望的候选者。在鼠和人的肌管中，Wnt7a激活合成代谢性AKT / mTOR途径，从而防止恶病质诱导的萎缩，单次施用足以独立于引起恶病质的肿瘤细胞类型预防萎缩。加入Wnt7a还可以改善癌症恶病质中肌肉干细胞的活化和分化，由于停滞的肌肉干细胞分化而严重损害骨骼肌再生的情况。最后，我们证明Wnt7a可以预防癌症恶病质C26结肠癌细胞的体内小鼠模型。Wnt7a在恶病质骨骼肌中起双重作用。也就是说，它可以通过激活合成代谢性AKT / mTOR途径有效抵消肌肉浪费，并且还可以逆转由于癌症恶病质而导致的肌肉干细胞功能丧失，从而使Wnt7a成为改善癌症恶病质的有前途的候选人。