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Cancers (Basel). 2019 Jul 30;11(8). pii: E1074. doi: 10.3390/cancers11081074.

The Transcriptional Roles of ALK Fusion Proteins in Tumorigenesis.

Author information

1
Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge CB20QQ, UK.
2
Department of Pathology, Medical University Vienna, 1090 Vienna, Austria.
3
Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge CB20QQ, UK. sdt36@cam.ac.uk.
4
Department of Pathology, Medical University Vienna, 1090 Vienna, Austria. gerda.egger@meduniwien.ac.at.
5
Ludwig Boltzmann Institute Applied Diagnostics, 1090 Vienna, Austria. gerda.egger@meduniwien.ac.at.

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.

KEYWORDS:

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

PMID:
31366041
DOI:
10.3390/cancers11081074
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