Lv Shihong, Chen Zhiye, Mi Hailong, Yu Xingjiang
Department of Gastroenterology, The Second Affiliated Hospital of Mudanjiang Medical College, Mudanjiang Medical College, Mudanjiang, 157011, People's Republic of China.
Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
Cancer Manag Res. 2022 Nov 24;14:3245-3269. doi: 10.2147/CMAR.S389825. eCollection 2022.
Cofilin, as a depolymerization factor of actin filaments, has been widely studied. Evidences show that cofilin has a role in actin structural reorganization and dynamic regulation. In recent years, several studies have demonstrated a regulatory role for cofilin in the migration and invasion mediated by cell dynamics and epithelial to mesenchymal transition (EMT)/EMT-like process, apoptosis, radiotherapy resistance, immune escape, and transcriptional dysregulation of malignant tumor cells, particularly glioma cells. On this basis, it is practical to evaluate cofilin as a biomarker for predicting tumor metastasis and prognosis. Targeting cofilin regulating kinases, Lin11, Isl-1 and Mec-3 kinases (LIM kinases/LIMKs) and their major upstream molecules inhibits tumor cell migration and invasion and targeting cofilin-mediated mitochondrial pathway induces apoptosis of tumor cells represent effective options for the development of novel anti-malignant tumor drug, especially anti-glioma drugs. This review explores the structure, general biological function, and regulation of cofilin, with an emphasis on the critical functions and prospects for clinical therapeutic applications of cofilin in malignant tumors represented by glioma.
丝切蛋白作为肌动蛋白丝的解聚因子，已得到广泛研究。证据表明，丝切蛋白在肌动蛋白结构重组和动态调节中发挥作用。近年来，多项研究证明丝切蛋白在细胞动力学介导的迁移和侵袭以及上皮-间质转化（EMT）/类EMT过程、凋亡、放疗抵抗、免疫逃逸和恶性肿瘤细胞尤其是胶质瘤细胞的转录失调中具有调节作用。在此基础上，将丝切蛋白评估为预测肿瘤转移和预后的生物标志物具有实际意义。靶向调节丝切蛋白的激酶，即Lin11、Isl-1和Mec-3激酶（LIM激酶/LIMKs）及其主要上游分子可抑制肿瘤细胞的迁移和侵袭，而靶向丝切蛋白介导的线粒体途径诱导肿瘤细胞凋亡是开发新型抗恶性肿瘤药物尤其是抗胶质瘤药物的有效选择。本综述探讨了丝切蛋白的结构、一般生物学功能及其调节，重点阐述了丝切蛋白在以胶质瘤为代表的恶性肿瘤中的关键功能及临床治疗应用前景。
