Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel.
Cancer Lett. 2020 Aug 1;484:65-71. doi: 10.1016/j.canlet.2020.04.016. Epub 2020 May 6.
Metabolic reprogramming is a characteristic feature of both cancer cells and their neighbouring cells in the tumor microenvironment (TME). The latter include stroma fibroblasts and adipocytes, that respectively differentiate to become cancer associated fibroblasts (CAFs) and cancer associated adipocytes (CAAs), and infiltrated immune cells, that collaborate with the stromal cells to provide the tumor a pro-tumorigenic niche. Here we discuss the association between the reprogramming of glucose metabolism in the TME and oncogenic signaling and its reflection in the non-canonical functions of metabolic enzymes. We also discuss the non-canonical actions of oncometabolites and the contribution to oncogenesis of external metabolites that accumulate in the TME as result of crosstalk between the tumor and the TME. Special emphasis is given in this regard to lysophosphatidic acid (LPA) and adenosine, two powerful metabolites, the concentrations of which rise in the TME due to altered metabolism of the tumor and its surrounding cells, allowing their action as external signals.
代谢重编程是肿瘤微环境（TME）中癌细胞及其邻近细胞的特征。后者包括基质成纤维细胞和脂肪细胞，它们分别分化为癌相关成纤维细胞（CAFs）和癌相关脂肪细胞（CAAs），以及浸润的免疫细胞，与基质细胞合作，为肿瘤提供有利于肿瘤发生的生态位。在这里，我们讨论了 TME 中葡萄糖代谢的重编程与致癌信号之间的关联及其在代谢酶非经典功能中的反映。我们还讨论了致癌代谢物的非经典作用，以及由于肿瘤与 TME 之间的串扰而在 TME 中积累的外部代谢物对肿瘤发生的贡献。在这方面特别强调了溶血磷脂酸（LPA）和腺苷这两种强大的代谢物，由于肿瘤及其周围细胞代谢的改变，它们在 TME 中的浓度升高，使它们能够作为外部信号发挥作用。
