Bueno Maura Lima Pereira, Saad Sara Teresinha Olalla, Roversi Fernanda Marconi
Hematology and Transfusion Medicine Center - University of Campinas/Hemocentro - UNICAMP, Campinas, São Paulo, Brazil.
Hematology and Transfusion Medicine Center - University of Campinas/Hemocentro - UNICAMP, Campinas, São Paulo, Brazil.
Biomed Pharmacother. 2022 Nov;155:113599. doi: 10.1016/j.biopha.2022.113599. Epub 2022 Sep 9.
The investigation of tumor microenvironment (TME) is essential to better characterize the complex cellular crosstalk and to identify important immunological phenotypes and biomarkers. The niche is a crucial contributor to neoplasm initiation, maintenance and progression. Therefore, a deeper analysis of tumor surroundings could improve cancer diagnosis, prognosis and assertive treatment. Thus, the WNT family exerts a critical action in tumorigenesis of different types of neoplasms due to dysregulations in the TME. WNT5A, an evolutionary WNT member, is involved in several cellular and physiopathological processes, in addition to tissue homeostasis. The WNT5A protein exerts paradoxical effects while acting as both an oncogene or tumor suppressor by regulating several non-canonical signaling pathways, and consequently interfering in cell growth, cytoskeletal remodeling, migration and invasiveness. This review focuses on a thorough characterization of the role of WNT5A in neoplastic transformation and progression, which may help to understand the prognostic potentiality of WNT5A and its features as a therapeutic target in several cancers. Additionally, we herein summarized novel findings on the mechanisms by which WNT5A might favor tumorigenesis or suppression of cancer progression and discussed the recently developed treatment strategies using WNT5A as a protagonist.
对肿瘤微环境(TME)的研究对于更好地表征复杂的细胞间相互作用以及识别重要的免疫表型和生物标志物至关重要。生态位是肿瘤发生、维持和进展的关键因素。因此,对肿瘤周围环境进行更深入的分析可以改善癌症的诊断、预后和精准治疗。因此,由于TME失调,WNT家族在不同类型肿瘤的发生中发挥着关键作用。WNT5A是一种进化上保守的WNT成员,除了参与组织稳态外,还参与多种细胞和生理病理过程。WNT5A蛋白通过调节多种非经典信号通路,既作为癌基因又作为肿瘤抑制因子发挥矛盾的作用,从而干扰细胞生长、细胞骨架重塑、迁移和侵袭。本综述着重全面阐述WNT5A在肿瘤转化和进展中的作用,这可能有助于理解WNT5A的预后潜力及其作为多种癌症治疗靶点的特征。此外,我们在此总结了关于WNT5A可能促进肿瘤发生或抑制癌症进展机制的新发现,并讨论了以WNT5A为主角的最新治疗策略。