中国科学院卜鹏程、朴海龙以及中国人民解放军总医院第七医学中心陈纲研究组合作取得最新进展。他们揭示肌酸通过激活Smad2/3促进肿瘤转移。2021年4月2日国际知名学术期刊《细胞-代谢》杂志发表了这一成果。

他们报告利用原位小鼠模型验证肌酸的不利影响，并表明肌酸促进结直肠癌和乳腺癌的转移，并缩短小鼠的生存期。他们表明，甘氨酸酰胺基转移酶（GATM）是肌酸合成限速酶，在肝转移中被上调。饮食摄取或GATM介导的肌酸从头合成，通过单极纺锤体1（MPS1）激活的Smad2和Smad3磷酸化上调了Snail和Slug的表达，从而增强了癌症的转移并缩短了小鼠的存活率。GATM敲低或MPS1抑制通过下调Snail和Slug抑制癌症转移并有益于小鼠存活。

他们的发现表明在考虑饮食中的肌酸以改善肌肉质量或治疗疾病时应谨慎行事，并建议靶向GATM或MPS1可预防癌症转移，尤其是转化生长因子β受体突变型结直肠癌的转移。

据了解，作为最受欢迎的营养补充剂之一，肌酸已被广泛用于增加肌肉质量和改善运动表现。

附：英文原文

Title: Creatine promotes cancer metastasis through activation of Smad2/3

Author: Liwen Zhang, Zijing Zhu, Huiwen Yan, Wen Wang, Zhenzhen Wu, Fei Zhang, Qixiang Zhang, Guizhi Shi, Junfeng Du, Huiyun Cai, Xuanxuan Zhang, David Hsu, Pu Gao, Hai-long Piao, Gang Chen, Pengcheng Bu

Issue&Volume: 2021-04-02

Abstract: As one of the most popular nutrient supplements, creatine has been highly used toincrease muscle mass and improve exercise performance. Here, we report an adverseeffect of creatine using orthotopic mouse models, showing that creatine promotes colorectaland breast cancer metastasis and shortens mouse survival. We show that glycine amidinotransferase(GATM), the rate-limiting enzyme for creatine synthesis, is upregulated in liver metastases.Dietary uptake, or GATM-mediated de novo synthesis of creatine, enhances cancer metastasis and shortens mouse survival byupregulation of Snail and Slug expression via monopolar spindle 1 (MPS1)-activatedSmad2 and Smad3 phosphorylation. GATM knockdown or MPS1 inhibition suppresses cancermetastasis and benefits mouse survival by downregulating Snail and Slug. Our findingscall for using caution when considering dietary creatine to improve muscle mass ortreat diseases and suggest that targeting GATM or MPS1 prevents cancer metastasis,especially metastasis of transforming growth factor beta receptor mutant colorectalcancers.

DOI: 10.1016/j.cmet.2021.03.009

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00116-9