Russell H. Morgan Department of Radiology and Radiological Science, Division of Interventional Radiology, The Johns Hopkins University School of Medicine , Baltimore, MD, USA.
Cancer Biol Ther. 2020 Oct 2;21(10):888-890. doi: 10.1080/15384047.2020.1809923. Epub 2020 Aug 31.
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 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.
肿瘤代谢的一个典型特征是葡萄糖利用率的增加，这是癌细胞的生化特征。糖酵解通量和戊糖磷酸途径 (PPP) 的增强所促进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 使细胞对治疗产生耐药性，特别是对 DNA 损伤的治疗药物。重要的是，这些发现表明 Rac1 依赖性化疗耐药性涉及糖酵解通量和 PPP 的上调。该研究使用多种方法证明，破坏 Rac1 的活性可使癌细胞对 DNA 损伤剂敏感。更重要的是，数据揭示了 Rac1 在乳腺癌中的 PPP 调节作用以前未知。最后，作者还展示了针对 Rac1 以增强乳腺癌化疗敏感性的有效性和可行性。这篇优雅的报告引发了人们的科学好奇心，促使我们进一步了解 Rac1 在癌症中的作用和调节的复杂性。
