Where Lactate to Go?——Effects of Exercise on Anti-tumor and Its Specificities

Lactate is a common metabolite of exercise and cancer cell. Lactate shuttle is a prerequisite for skeletal muscles to rapidly synthesize ATP during exercise and maintain their contraction ability. The negative correlation between exercise and cancer risks has been well established, however, there is a conflict in the process of lactate metabolism, i.e., exercise promotes the turnover of lactate between muscle and other tissues, while“anti-tumor”requires reducing or even cutting off the lactate shuttle. Four conflicts related to lactate metabolism were firstly proposed as following: 1) The advantages or disadvantages of exercise-induced lactate to tumor microenvironment; 2) The advantages or disadvantages of exercise-activated lactate dehydrogenase to tumor growth; 3) Does mitochondrial lactate metabolism recycle muscle's carbon sources or promote tumor growth?4) Does lactate-induced fat browning improve metabolism or exacerbate cancer associated cachexia? To resolve these conflicts, the lactate exchanges between muscles,liver, blood and cancer cells were discussed in this review. Four hypotheses on lactate threshold were proposed to further understand the specificity of exercise in anti-tumor, and future directions and suggestions were also proposed for the personalized anti-tumor strategy.