Fondazione Italiana Fegato - ONLUS, Liver Cancer Unit, Trieste, Italy.
Department of Life Sciences, Università degli Studi di Trieste, Trieste, Italy.
Cell Prolif. 2024 Aug;57(8):e13641. doi: 10.1111/cpr.13641. Epub 2024 Apr 8.
Aurora Kinase A (AURKA) plays a central role as a serine/threonine kinase in regulating cell cycle progression and mitotic functions. Over the years, extensive research has revealed the multifaceted roles of AURKA in cancer development and progression. AURKA's dysregulation is frequently observed in various human cancers, including hepatocellular carcinoma (HCC). Its overexpression in HCC has been associated with aggressive phenotypes and poor clinical outcomes. This review comprehensively explores the molecular mechanisms underlying AURKA expression in HCC and its functional implications in cell migration, invasion, epithelial-to-mesenchymal transition, metastasis, stemness, and drug resistance. This work focuses on the clinical significance of AURKA as a diagnostic and prognostic biomarker for HCC. High levels of AURKA expression have been correlated with shorter overall and disease-free survival in various cohorts, highlighting its potential utility as a sensitive prognostic indicator. Recent insights into AURKA's role in modulating the tumour microenvironment, particularly immune cell recruitment, may provide valuable information for personalized treatment strategies. AURKA's critical involvement in modulating cellular pathways and its overexpression in cancer makes it an attractive target for anticancer therapies. This review discusses the evidence about novel and selective AURKA inhibitors for more effective treatments for HCC.
极光激酶 A(AURKA)作为丝氨酸/苏氨酸激酶,在调节细胞周期进程和有丝分裂功能方面发挥着核心作用。多年来,广泛的研究揭示了 AURKA 在癌症发展和进展中的多方面作用。AURKA 的失调在包括肝细胞癌(HCC)在内的各种人类癌症中经常观察到。其在 HCC 中的过表达与侵袭性表型和不良临床结局相关。本综述全面探讨了 HCC 中 AURKA 表达的分子机制及其在细胞迁移、侵袭、上皮-间充质转化、转移、干性和耐药性方面的功能意义。这项工作重点关注 AURKA 作为 HCC 诊断和预后生物标志物的临床意义。在多个队列中,AURKA 表达水平较高与总生存期和无病生存期较短相关,突出了其作为敏感预后指标的潜在效用。最近对 AURKA 在调节肿瘤微环境(特别是免疫细胞募集)中的作用的深入了解可能为个性化治疗策略提供有价值的信息。AURKA 在调节细胞通路中的关键作用及其在癌症中的过表达使其成为抗癌治疗的有吸引力的靶点。本综述讨论了关于新型和选择性 AURKA 抑制剂的证据,以期为 HCC 提供更有效的治疗方法。