ALK pERKs up MYCN in neuroblastoma.

Abstract

The gene expressing the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) is mutated and aberrantly expressed in several cancers. The clinical efficacy of the ALK inhibitor, crizotinib, lags behind expectations for treating MYCN-amplified, ALK-mutant neuroblastoma, a deadly childhood cancer. In this issue of Science Signaling, Umapathy et al. identify the kinase extracellular signal-regulated kinase 5 (ERK5) as a central mediator that enables ALK to boost MYCN expression, and they show that inhibiting ERK5 in concert with ALK reduced neuroblastoma cell viability in vitro and in xenograft tumor models. This report has important clinical implications for the treatment of patients with neuroblastoma or other tumors that overexpress MYC(N) and harbor ALK mutations, such as non-small-cell lung cancer.

• Authors: Sven Lindner, Anton Henssen, Kathy Astrahantseff, Johannes H Schulte
• Journal: Science signaling (Sci Signal) Vol. 7 Issue 349 Pg. pe27 (Oct 28 2014) ISSN: 1937-9145 [Electronic] United States
• PMID: 25351246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014, American Association for the Advancement of Science.

Chemical References

• MYCN protein, human
• N-Myc Proto-Oncogene Protein
• Nuclear Proteins
• Oncogene Proteins
• ALK protein, human
• Anaplastic Lymphoma Kinase
• Receptor Protein-Tyrosine Kinases
• Mitogen-Activated Protein Kinase 7

Topics

• Anaplastic Lymphoma Kinase
• Gene Expression Regulation, Neoplastic (genetics, physiology)
• Humans
• Mitogen-Activated Protein Kinase 7 (metabolism)
• Mutation (genetics)
• N-Myc Proto-Oncogene Protein
• Neuroblastoma (genetics)
• Nuclear Proteins (metabolism)
• Oncogene Proteins (metabolism)
• Receptor Protein-Tyrosine Kinases (genetics, metabolism)
• Signal Transduction (physiology)