Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.
APMIS. 2024 Dec;132(12):906-927. doi: 10.1111/apm.13447. Epub 2024 Jun 14.
Cancer-associated fibroblasts (CAFs) are crucial component of tumor microenvironment (TME) which undergo significant phenotypic changes and metabolic reprogramming, profoundly impacting tumor growth. This review delves into CAF plasticity, diverse origins, and the molecular mechanisms driving their continuous activation. Emphasis is placed on the intricate bidirectional crosstalk between CAFs and tumor cells, promoting cancer cell survival, proliferation, invasion, and immune evasion. Metabolic reprogramming, a cancer hallmark, extends beyond cancer cells to CAFs, contributing to the complex metabolic interplay within the TME. The 'reverse Warburg effect' in CAFs mirrors the Warburg effect, involving the export of high-energy substrates to fuel cancer cells, supporting their rapid proliferation. Molecular regulations by key players like p53, Myc, and K-RAS orchestrate this metabolic adaptation. Understanding the metabolic symbiosis between CAFs and tumor cells opens avenues for targeted therapeutic strategies to disrupt this dynamic crosstalk. Unraveling CAF-mediated metabolic reprogramming provides valuable insights for developing novel anticancer therapies. This comprehensive review consolidates current knowledge, shedding light on CAFs' multifaceted roles in the TME and offering potential targets for future therapies.
癌症相关成纤维细胞（CAFs）是肿瘤微环境（TME）的重要组成部分，经历了显著的表型变化和代谢重编程，深刻影响着肿瘤的生长。本综述深入探讨了 CAF 的可塑性、多种起源以及驱动其持续激活的分子机制。重点强调了 CAFs 与肿瘤细胞之间复杂的双向串扰，促进了癌细胞的存活、增殖、侵袭和免疫逃逸。代谢重编程是癌症的一个标志，不仅限于癌细胞，还延伸到 CAFs，为 TME 内的复杂代谢相互作用做出了贡献。CAFs 中的“反向沃伯格效应”反映了沃伯格效应，涉及高能底物的输出以为肿瘤细胞提供燃料，支持其快速增殖。关键分子如 p53、Myc 和 K-RAS 的调节作用协调了这种代谢适应。理解 CAFs 与肿瘤细胞之间的代谢共生关系为靶向治疗策略的发展提供了打破这种动态串扰的途径。揭示 CAF 介导的代谢重编程为开发新型抗癌疗法提供了有价值的见解。本综述综合了当前的知识，阐明了 CAFs 在 TME 中的多方面作用，并为未来的治疗提供了潜在的靶点。
