Ducray Stephen P, Natarajan Karthikraj, Garland Gavin D, Turner Suzanne D, Egger Gerda
Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge CB20QQ, UK.
Department of Pathology, Medical University Vienna, 1090 Vienna, Austria.
Cancers (Basel). 2019 Jul 30;11(8):1074. doi: 10.3390/cancers11081074.
Anaplastic lymphoma kinase (ALK) is a tyrosine kinase involved in neuronal and gut development. Initially discovered in T cell lymphoma, ALK is frequently affected in diverse cancers by oncogenic translocations. These translocations involve different fusion partners that facilitate multimerisation and autophosphorylation of ALK, resulting in a constitutively active tyrosine kinase with oncogenic potential. ALK fusion proteins are involved in diverse cellular signalling pathways, such as Ras/extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K)/Akt and Janus protein tyrosine kinase (JAK)/STAT. Furthermore, ALK is implicated in epigenetic regulation, including DNA methylation and miRNA expression, and an interaction with nuclear proteins has been described. Through these mechanisms, ALK fusion proteins enable a transcriptional programme that drives the pathogenesis of a range of ALK-related malignancies.
间变性淋巴瘤激酶（ALK）是一种参与神经元和肠道发育的酪氨酸激酶。ALK最初在T细胞淋巴瘤中被发现，在多种癌症中常因致癌性易位而受到影响。这些易位涉及不同的融合伴侣，促进ALK的多聚化和自磷酸化，产生具有致癌潜力的组成型活性酪氨酸激酶。ALK融合蛋白参与多种细胞信号通路，如Ras/细胞外信号调节激酶（ERK）、磷脂酰肌醇3激酶（PI3K）/Akt和Janus蛋白酪氨酸激酶（JAK）/STAT。此外，ALK还参与表观遗传调控，包括DNA甲基化和miRNA表达，并且已描述了其与核蛋白的相互作用。通过这些机制，ALK融合蛋白启动一个转录程序，驱动一系列ALK相关恶性肿瘤的发病机制。
