Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan 450052, China.
Theranostics. 2021 Jul 13;11(17):8322-8336. doi: 10.7150/thno.62378. eCollection 2021.
Cancer cells are well-known for adapting their metabolism to maintain high proliferation rates and survive in unfavorable environments with low oxygen and nutritional deficiency. Metabolic reprogramming most commonly arises from the tumor microenvironment (TME). The events of metabolic pathways include the Warburg effect, shift in Krebs cycle metabolites, and increase rate of oxidative phosphorylation that provides the energy for the development and invasion of cancer cells. The TME and shift in tumor metabolism shows a close relationship through bidirectional signaling pathways between the stromal and tumor cells. Cancer-associated fibroblasts (CAFs) are the main type of stromal cells in the TME and consist of a heterogeneous and plastic population that play key roles in tumor growth and metastatic capacity. Emerging evidence suggests that CAFs act as major regulators in shaping tumor metabolism especially through the dysregulation of several metabolic pathways, including glucose, amino acid, and lipid metabolism. The arrangement of these metabolic switches is believed to shape distinct CAF behavior and change tumor cell behavior by the CAFs. The crosstalk between cancer cells and CAFs is associated with cell metabolic reprogramming that contributes to cancer cell growth, progression, and evasion from cancer therapies. But the mechanism and process of this interaction remain unclear. This review aimed to highlight the metabolic couplings between tumor cells and CAFs. We reviewed the recent literature supporting an important role of CAFs in the regulation of cancer cell metabolism, and the relevant pathways, which may serve as targets for therapeutic interventions.
癌细胞以适应代谢来维持高增殖率并在低氧和营养缺乏的不利环境中存活而闻名。代谢重编程最常见于肿瘤微环境 (TME)。代谢途径的事件包括瓦博格效应、克雷布斯循环代谢物的转移以及氧化磷酸化速率的增加，为癌细胞的发展和侵袭提供能量。TME 和肿瘤代谢的转变通过基质细胞和肿瘤细胞之间的双向信号通路显示出密切的关系。癌症相关成纤维细胞 (CAFs) 是 TME 中主要的基质细胞类型，由异质和可塑性的群体组成，在肿瘤生长和转移能力中发挥关键作用。新出现的证据表明，CAFs 通过调节包括葡萄糖、氨基酸和脂质代谢在内的几种代谢途径，作为主要的调节因子在塑造肿瘤代谢中发挥作用。这些代谢开关的排列被认为可以塑造不同的 CAF 行为，并通过 CAFs 改变肿瘤细胞的行为。癌细胞和 CAFs 之间的串扰与细胞代谢重编程有关，这有助于癌细胞的生长、进展和逃避癌症治疗。但这种相互作用的机制和过程尚不清楚。本综述旨在强调肿瘤细胞和 CAFs 之间的代谢耦合。我们回顾了最近的文献，这些文献支持 CAFs 在调节癌细胞代谢中的重要作用，以及相关的途径，这些途径可能成为治疗干预的靶点。
