Research ArticleCancer

The kinase ALK stimulates the kinase ERK5 to promote the expression of the oncogene MYCN in neuroblastoma

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Science Signaling  28 Oct 2014:
Vol. 7, Issue 349, pp. ra102
DOI: 10.1126/scisignal.2005470

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A New Target in Neuroblastoma

Neuroblastoma is a common and aggressive pediatric cancer caused by various molecular abnormalites. Similar to other cancers, poor prognosis correlates with increased abundance or activation of the cell surface receptor tyrosine kinase ALK or increased abundance of the transcription factor MYCN. An ALK inhibitor used in the clinic is not wholly effective, and there are no therapies to directly target MYCN. Umapathy et al. found that ALK stimulated the expression of the gene encoding MYCN through a pathway involving several kinases in patient tumor cells. Targeting one of these kinases, ERK5, decreased the abundance of MYCN and suppressed proliferation in ALK-positive neuroblastoma cells in culture. Combined inhibition of ALK and ERK5 was more effective than the ALK inhibitor alone in limiting tumor growth in a mouse model. Thus, ERK5 represents a new target for treating ALK-driven cancers.

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