The Role of Cancer⁃Associated Fibroblasts (Cafs) In Tumor Development

Today, cancer is still the key threaten to life, and CAFs are one of the mostly studied risk factor. This article reviews the mechanism of respiration of CAFS cells in cancer like Reverse Warburg Effect of CAFs, as well as the mechanism of TGF-β/Smad, the related diseases and corresponding drugs by targeting CAFs production. In tumor microenvironment(TME), CAFs are closely associated with the development, transfer and aggression of tumor cells. ‘Reverse Warburg Effect is one of the ways for CAFs to achieve metabolic cross-talk with tumor cells. Through oxidative glycolysis, CAFs can produce plenty of energy-rich substrate, like pyruvate, fat acid and lactate, those substrates are transported to mitochondria in tumor cells in order to produce many ATP by OXPHOS. Besides, CAFs transfer lactate in hypoxia by MCT4 and then MCT1 on tumor cells surface, which can support themselves. In addition, the TGF-β/Smad, the main pathway promoting the development of CAFs and tumor cells, is also dissected. By conducting a thorough analysis on the mechanism of TGF-β based malignant cells and CAFs production, the relevant drugs are introduced. Those findings can not only enhance our understanding of the complexity of tumor metabolism, but it also provides a theoretical basis for the development of new therapeutic strategies and potential targets.