Trejo-Solis Cristina, Escamilla-Ramirez Angel, Jimenez-Farfan Dolores, Castillo-Rodriguez Rosa Angelica, Flores-Najera Athenea, Cruz-Salgado Arturo
Laboratorio Experimental de Enfermedades Neurodegenerativas, Instituto Nacional de Neurología y Neurocirugía, Ciudad de Mexico 14269, Mexico.
Laboratorio de Inmunología, División de Estudios de Posgrado e Investigación, Facultad de Odontología, Universidad Nacional Autónoma de México, Ciudad de Mexico 04510, Mexico.
Pharmaceuticals (Basel). 2021 Aug 28;14(9):871. doi: 10.3390/ph14090871.
The Wnt/β-catenin signaling pathway plays a major role in cell survival and proliferation, as well as in angiogenesis, migration, invasion, metastasis, and stem cell renewal in various cancer types. However, the modulation (either up- or downregulation) of this pathway can inhibit cell proliferation and apoptosis both through β-catenin-dependent and independent mechanisms, and by crosstalk with other signaling pathways in a wide range of malignant tumors. Existing studies have reported conflicting results, indicating that the Wnt signaling can have both oncogenic and tumor-suppressing roles, depending on the cellular context. This review summarizes the available information on the role of the Wnt/β-catenin pathway and its crosstalk with other signaling pathways in apoptosis induction in cancer cells and presents a modified dual-signal model for the function of β-catenin. Understanding the proapoptotic mechanisms induced by the Wnt/β-catenin pathway could open new therapeutic opportunities.
Wnt/β-连环蛋白信号通路在细胞存活、增殖以及多种癌症类型的血管生成、迁移、侵袭、转移和干细胞更新中发挥着主要作用。然而,该信号通路的调节(上调或下调)可通过β-连环蛋白依赖性和非依赖性机制,以及在多种恶性肿瘤中与其他信号通路的相互作用,抑制细胞增殖和凋亡。现有研究报告的结果相互矛盾,表明Wnt信号根据细胞环境可具有致癌和抑癌双重作用。本综述总结了关于Wnt/β-连环蛋白通路在癌细胞凋亡诱导中的作用及其与其他信号通路相互作用的现有信息,并提出了一种关于β-连环蛋白功能的改良双信号模型。了解Wnt/β-连环蛋白通路诱导的促凋亡机制可能会带来新的治疗机会。