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The Transcriptional Roles of ALK Fusion Proteins in Tumorigenesis

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CANCERS
卷 11, 期 8, 页码 -

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MDPI
DOI: 10.3390/cancers11081074

关键词

ALK; ALCL; NPM-ALK; EML4-ALK; NSCLC; ALK-translocation proteins; epigenetics

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  1. European Union's Horizon 2020 Marie Sklodowska-Curie Innovative Training Networks (ITN-ETN) [675712]

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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.

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