The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing 100050, China; Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing 100050, China; Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China.
Gene. 2024 Mar 1;897:148079. doi: 10.1016/j.gene.2023.148079. Epub 2023 Dec 13.
The Forkhead box C1 (FOXC1) transcription factor is an important member of the FOX family. After initially being identified in triple-negative breast cancer (TNBC) with significant oncogenic function, FOXC1 was subsequently demonstrated to be involved in the development of more than 16 types of cancers. In recent years, increasing studies have focused on the deregulatory mechanisms of FOXC1 expression and revealed that FOXC1 expression was regulated at multiple levels including transcriptional regulation, post-transcription regulation and post-translational modification. Moreover, dysregulation of FOXC1 is also implicated in drug resistance in various types of cancer, especially in breast cancer, which further emphasizes the translational and clinical significance of FOXC1 as a therapeutic target in cancer treatment. This review summarizes recent findings on mechanisms of FOXC1 dysregulation in cancers and its role in chemoresistance, which will help to better understand the oncogenic role of FOXC1, overcome FOXC1-mediated drug resistance and develop targeted therapy for FOXC1 in cancers.
叉头框蛋白 C1(FOXC1)转录因子是 FOX 家族的重要成员。FOXC1 最初在三阴性乳腺癌(TNBC)中被鉴定具有显著的致癌功能,随后被证明参与了超过 16 种癌症的发生发展。近年来,越来越多的研究集中在 FOXC1 表达的失调机制上,揭示了 FOXC1 的表达受到多个层面的调控,包括转录调控、转录后调控和翻译后修饰。此外,FOXC1 的失调也与多种癌症的耐药性有关,尤其是在乳腺癌中,这进一步强调了 FOXC1 作为癌症治疗靶点的转化和临床意义。本综述总结了 FOXC1 失调在癌症中的机制及其在化疗耐药中的作用的最新发现,这将有助于更好地理解 FOXC1 的致癌作用,克服 FOXC1 介导的耐药性,并开发针对癌症中 FOXC1 的靶向治疗。