Zhang Xiaoyan, Zhang Meng, Sun Hui, Wang Xu, Wang Xin, Sheng Weiqi, Xu Midie
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Institute of Pathology, Fudan University, Shanghai 200032, China.
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Institute of Pathology, Fudan University, Shanghai 200032, China.
J Adv Res. 2025 Jan;67:121-132. doi: 10.1016/j.jare.2024.01.033. Epub 2024 Feb 2.
Transcription factors (TFs) fulfill a critical role in the formation and maintenance of different cell types during the developmental process as well as disease. It is believed that cancer-associated fibroblasts (CAFs) are activation status of tissue-resident fibroblasts or derived from form other cell types via transdifferentiation or dedifferentiation. Despite a subgroup of CAFs exhibit anti-cancer effects, most of them are reported to exert effects on tumor progression, further indicating their heterogeneous origin.
This review aimed to summarize and review the roles of TFs in the reciprocal crosstalk between CAFs and tumor cells, discuss the emerging mechanisms, and their roles in cell-fate decision, cellular reprogramming and advancing our understanding of the gene regulatory networks over the period of cancer initiation and progression.
This manuscript delves into the key contributory factors of TFs that are involved in activating CAFs and maintaining their unique states. Additionally, it explores how TFs play a pivotal and multifaceted role in the reciprocal crosstalk between CAFs and tumor cells. This includes their involvement in processes such as epithelial-mesenchymal transition (EMT), proliferation, invasion, and metastasis, as well as metabolic reprogramming. TFs also have a role in constructing an immunosuppressive microenvironment, inducing resistance to radiation and chemotherapy, facilitating angiogenesis, and even 'educating' CAFs to support the malignancies of tumor cells. Furthermore, this manuscript delves into the current status of TF-targeted therapy and considers the future directions of TFs in conjunction with anti-CAFs therapies to address the challenges in clinical cancer treatment.
转录因子（TFs）在发育过程以及疾病中不同细胞类型的形成和维持中发挥着关键作用。据信，癌症相关成纤维细胞（CAFs）是组织驻留成纤维细胞的激活状态，或者是通过转分化或去分化从其他细胞类型衍生而来。尽管有一部分CAFs具有抗癌作用，但据报道大多数CAFs会对肿瘤进展产生影响，这进一步表明它们起源的异质性。
本综述旨在总结和回顾转录因子在CAFs与肿瘤细胞相互串扰中的作用，讨论新出现的机制，以及它们在细胞命运决定、细胞重编程中的作用，并增进我们对癌症起始和进展过程中基因调控网络的理解。
本手稿深入探讨了参与激活CAFs并维持其独特状态的转录因子的关键促成因素。此外，还探讨了转录因子如何在CAFs与肿瘤细胞的相互串扰中发挥关键且多方面的作用。这包括它们参与上皮-间质转化（EMT）、增殖、侵袭和转移等过程，以及代谢重编程。转录因子还在构建免疫抑制微环境、诱导对放疗和化疗的抗性、促进血管生成，甚至“驯化”CAFs以支持肿瘤细胞的恶性生长方面发挥作用。此外，本手稿深入探讨了靶向转录因子治疗的现状，并结合抗CAFs疗法考虑转录因子的未来方向，以应对临床癌症治疗中的挑战。
