卜鹏程等Cell子刊突破:膳食补充剂肌酸如何促进癌症转移
创作:mildbreeze 审核:mildbreeze 05月01日
  • 在原位肿瘤小鼠模型中,补充肌酸促进结直肠癌(CRC)和乳腺癌的转移,缩短生存期;
  • 甘氨酸脒基转移酶(GATM,肌酸合成的限速酶)在CRC和乳腺癌转移组织中高表达,且GATM表达越高,患者预后越差,高表达GATM促进CRC发生肝转移;
  • 补充膳食肌酸,或由GATM介导的肌酸从头合成,能够通过单极纺锤体1激酶(MPS1,而非TGF-β受体)活化Smad2/3,上调肿瘤细胞中Snail和Snug的表达,从而促进CRC和乳腺癌的转移、缩短小鼠生存期;
  • 敲低GATM、抑制GATM酶活或抑制MPS1活性,能够抑制小鼠肿瘤的转移。
主编推荐语
mildbreeze
肌酸是一种营养补充剂,能够辅助为肌肉和神经细胞提供能量,尤其在健身爱好者和运动员中被广泛使用。中科院生物物理研究所卜鹏程团队、中国人民解放军总医院第七医学中心陈纲团队与中科院大连化学物理研究所朴海龙团队合作,在Cell Metabolism发表的最新研究中却发现,体外补充或者体内合成肌酸可增强癌症转移。该研究通过细胞实验、多种小鼠模型实验以及分析患者样本充分证实,由外源性补充或由GATM介导的内源性合成所引起的肿瘤内肌酸水平升高,可经MPS1活化Smad2/3来上调Slug和Snail的表达,从而促进肿瘤转移。这些发现不仅警示癌症患者或高危人群应谨慎使用肌酸补充剂,也为预防由肌酸介导的癌症转移提供了潜在的干预靶点。
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Cell Metabolism [IF:21.567]

Creatine promotes cancer metastasis through activation of Smad2/3

肌酸通过活化Smad2/3促进癌症转移

10.1016/j.cmet.2021.03.009

04-02, Article

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As one of the most popular nutrient supplements, creatine has been highly used to increase muscle mass and improve exercise performance. Here, we report an adverse effect of creatine using orthotopic mouse models, showing that creatine promotes colorectal and 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 by upregulation of Snail and Slug expression via monopolar spindle 1 (MPS1)-activated Smad2 and Smad3 phosphorylation. GATM knockdown or MPS1 inhibition suppresses cancer metastasis and benefits mouse survival by downregulating Snail and Slug. Our findings call for using caution when considering dietary creatine to improve muscle mass or treat diseases and suggest that targeting GATM or MPS1 prevents cancer metastasis, especially metastasis of transforming growth factor beta receptor mutant colorectal cancers.

First Authors:
Liwen Zhang

Correspondence Authors:
Hai-long Piao,Gang Chen,Pengcheng Bu

All Authors:
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

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