Abstract：
Metastasis is the leading cause of cancer-related deaths, making the development of novel, more effective therapies imperative to alleviate patient suffering. Metabolic switching is a hallmark of cancer cells that facilitates metastasis. Cancer cells obtain most of their energy and intermediate metabolites, which are required to proliferate and metastasize, through aerobic glycolysis. Previous work from our laboratory has shown that Caveolin-1 (CAV1) expression in cancer cells promotes glycolysis and metastasis. Here, we sought to determine if limiting glycolysis reduced CAV1-enhanced metastasis and to identify the mechanism(s) involved. We evaluated the effects of the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) in metastatic melanoma and breast cancer cell lines expressing or not CAV1. Non-cytotoxic concentrations of 2-DG (1 mM) inhibited the migration of B16-F10 melanoma and MDA-MB-231 breast cancer cells. CAV1-mediated activation of Src/Akt signaling was required for CAV1-enhanced migration and was blocked in the presence of 2-DG. Moreover, inhibition of Akt reduced CAV1-enhanced lung metastasis of B16-F10 cells. Collectively, these findings highlight the importance of CAV1-induced metabolic reprogramming for metastasis and point towards possible therapeutic approaches to prevent metastatic disease by inhibiting glycolysis and Src/Akt signaling.
摘要：
转移是癌症相关死亡的主要原因，使小说的发展，更有效的治疗方法必须减轻患者的痛苦。代谢转换是促进转移的癌细胞的标志。癌细胞获得大部分能量和中间代谢物，它们是增殖和转移所必需的，通过有氧糖酵解。我们实验室的先前工作表明，癌细胞中的Caveolin-1（CAV1）表达促进糖酵解和转移。这里,我们试图确定限制糖酵解是否减少了CAV1增强的转移，并确定了相关机制。我们评估了糖酵解抑制剂2-脱氧-D-葡萄糖（2-DG）在表达或不表达CAV1的转移性黑色素瘤和乳腺癌细胞系中的作用。非细胞毒性浓度的2-DG（1mM）抑制B16-F10黑色素瘤和MDA-MB-231乳腺癌细胞的迁移。CAV1介导的Src/Akt信号的激活是CAV1增强的迁移所必需的，并且在2-DG存在下被阻断。此外，抑制Akt可减少CAV1增强的B16-F10细胞的肺转移。总的来说，这些发现强调了CAV1诱导的代谢重编程对转移的重要性,并指出了通过抑制糖酵解和Src/Akt信号传导来预防转移性疾病的可能治疗方法.
