The Transcriptional Roles of ALK Fusion Proteins in Tumorigenesis

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2019 Aug 2

PMID 31366041

Citations 40

Authors

Stephen P Ducray

Karthikraj Natarajan

Gavin D Garland

Suzanne D Turner

Gerda Egger

Affiliations

Soon will be listed here.

Abstract

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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