细胞外代谢能量可以促进癌症的进展
Jia Min Loo1, Alexis Scherl1, Alexander Nguyen1
1Laboratory of Systems Cancer Biology, Rockefeller University, New York, NY 10065, USA.
Cell
|January 21, 2015
概括
两个微RNA,miR-551a和miR-483,通过向大脑类型 (CKB) 的肌酸激酶,抑制肝转移. 这些miRNAs或CKB抑制的治疗治疗减少了结直肠癌的传播,突出了新的代谢脆弱性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 代谢过程中的代谢.
背景情况:
- 大肠直肠癌经常转移到肝脏,每年造成超过60万人的死亡.
- 微RNAs (miRNAs) 在癌症的进展和转移中起着至关重要的作用.
- 代谢重编程是癌症的标志,支持瘤生长和生存.
研究的目的:
- 在结直肠癌中识别肝脏殖民和转移的内源性抑制剂.
- 阐明这些抑制剂调节癌细胞代谢的分子机制.
- 评估针对已识别的抑制剂或其下游效应物的治疗潜力.
主要方法:
- 在肝脏殖民期间对661个微RNA (miRNA) 的功能查.
- 通过miR-551a和miR-483.3研究肌酸激酶,脑型 (CKB) 的融合向.
- 评估细胞外CKB和肌酸载体SLC6A8在转移细胞ATP生成中的作用.
- 在体内评估miRNAs病毒传递和CKB抑制的治疗疗效.
主要成果:
- 确定miR-551a和miR-483是肝脏殖民和转移的强有力的抑制剂.
- 这些miRNAs向CKB,这是一种对脂蛋白产生至关重要的酶,为转移性ATP生成提供燃料.
- 在人肝转移中,细胞外CKB和SLC6A8被上调,而miR-551a/miR-483被下调.
- 在体内,miR-551a/miR-483或CKB抑制的治疗性输送显著抑制了转移.
结论:
- miR-551a和miR-483是结直肠癌肝脏转移的关键内源调节剂.
- 针对细胞外CKB介导的代谢途径是一个有前途的治疗策略.
- 细胞外空间是转移的代谢支持的关键部分,也是一个可行的治疗点.
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