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Rac1 repression reverses chemoresistance by targeting tumor metabolism.
Cancer Biology & Therapy ( IF 4.4 ) Pub Date : 2020-08-31 , DOI: 10.1080/15384047.2020.1809923
Shanmugasundaram Ganapathy-Kanniappan 1
Affiliation  

ABSTRACT

Tumor metabolism is exemplified by the increased rate of glucose utilization, a biochemical signature of cancer cells. The enhanced glucose hydrolysis enabled by the augmentation of glycolytic flux and the pentose phosphate pathway (PPP) plays a pivotal role in the growth and survival of neoplastic cells. In a recent report, it has been shown that in human breast cancer the GTP binding protein, Rac1 enables resistance to therapy, particularly against the DNA-damaging therapeutics. Significantly, the findings demonstrate that Rac1-dependent chemoresistance involves the upregulation of glycolytic flux as well as PPP. Using multiple approaches, the study demonstrates that disruption of Rac1 activity sensitizes cancer cells to DNA-damaging agents. More importantly, the data uncover a previously unknown PPP regulatory role of Rac1 in breast cancer. Finally, the authors also show the effectiveness and the feasibility of in vivo targeting of Rac1 to enhance the chemosensitivity of breast cancer. This elegant report provokes scientific curiosity to expand our understanding of the intricacies of the role and regulation of Rac1 in cancer.



中文翻译:

Rac1 抑制通过靶向肿瘤代谢逆转化学抗性。

摘要

肿瘤代谢的例子是葡萄糖利用率的增加,这是癌细胞的生化特征。通过增加糖酵解通量和戊糖磷酸途径 (PPP) 实现的增强的葡萄糖水解在肿瘤细胞的生长和存活中起着关键作用。在最近的一份报告中,已经表明,在人类乳腺癌中,GTP 结合蛋白 Rac1 能够抵抗治疗,尤其是对 DNA 损伤疗法的抵抗。重要的是,研究结果表明,Rac1 依赖性化学抗性涉及糖酵解通量和 PPP 的上调。该研究使用多种方法表明,Rac1 活性的破坏会使癌细胞对 DNA 损伤剂敏感。更重要的是,这些数据揭示了 Rac1 在乳腺癌中的一种以前未知的 PPP 调节作用。体内靶向 Rac1 以增强乳腺癌的化学敏感性。这份优雅的报告激发了科学的好奇心,以扩大我们对 Rac1 在癌症中的作用和调节的复杂性的理解。

更新日期:2020-10-20
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