The Transcriptional Roles of ALK Fusion Proteins in Tumorigenesis

Cancers
Stephen P DucrayGerda Egger

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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Citations

Jul 9, 2020·Frontiers in Oncology·Yumeng ZhangLubomir Sokol
Apr 15, 2020·Cancers·Abdulaziz B Hamid, Ruben C Petreaca
Nov 11, 2020·Epigenetics & Chromatin·Wen-Jun WangJiu-Wei Cui
Jan 3, 2021·Journal of Cancer Research and Clinical Oncology·Mian LiuShi Chang
Jul 11, 2020·Cell·Michael A GilletteUNKNOWN Clinical Proteomic Tumor Analysis Consortium
Feb 5, 2021·The Journal of Applied Laboratory Medicine·Yu-Wei ChengBrian P Rubin
Jan 21, 2021·Cancers·Elissa AndraosFabienne Meggetto
Nov 18, 2020·International Journal of Molecular Sciences·Jorge Esteban-VillarrubiaJavier Molina-Cerrillo
Mar 12, 2021·Frontiers in Oncology·Zhengqi WenHushan Zhang

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Methods Mentioned

BETA
immunoprecipitation
nuclear translocation

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