Frenquelli Michela, Tonon Giovanni
B-cell Neoplasia Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Functional Genomics of Cancer Unit, Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Front Oncol. 2020 Dec 21;10:615190. doi: 10.3389/fonc.2020.615190. eCollection 2020.
The role of the WNT signaling pathway in key cellular processes, such as cell proliferation, differentiation and migration is well documented. WNT signaling cascade is initiated by the interaction of WNT ligands with receptors belonging to the Frizzled family, and/or the ROR1/ROR2 and RYK families. The downstream signaling cascade results in the activation of the canonical β-catenin dependent pathway, ultimately leading to transcriptional control of cell proliferation, or the non-canonical pathway, mainly acting on cell migration and cell polarity. The high level of expression of both WNT ligands and WNT receptors in cancer cells and in the surrounding microenvironment suggests that WNT may represent a central conduit of interactions between tumor cells and microenviroment. In this review we will focus on WNT pathways deregulation in hematological cancers, both at the ligand and receptor levels. We will review available literature regarding both the classical β-catenin dependent pathway as well as the non-canonical pathway, with particular emphasis on the possible exploitation of WNT aberrant activation as a therapeutic target, a notion supported by preclinical data.
WNT信号通路在细胞增殖、分化和迁移等关键细胞过程中的作用已有充分记载。WNT信号级联反应由WNT配体与属于卷曲蛋白家族、ROR1/ROR2家族和RYK家族的受体相互作用引发。下游信号级联反应导致经典的β-连环蛋白依赖性途径激活，最终导致对细胞增殖的转录控制，或非经典途径激活，主要作用于细胞迁移和细胞极性。癌细胞及其周围微环境中WNT配体和WNT受体的高表达水平表明，WNT可能是肿瘤细胞与微环境之间相互作用的核心通道。在本综述中，我们将聚焦于血液系统恶性肿瘤中WNT通路在配体和受体水平的失调。我们将回顾关于经典β-连环蛋白依赖性途径以及非经典途径的现有文献，特别强调将WNT异常激活作为治疗靶点的可能性，临床前数据支持这一观点。
