Neuronal leucine-rich repeat 1 negatively regulates anaplastic lymphoma kinase in neuroblastoma.
Sci Rep. 2016 09 08;6:32682
Authors: Satoh S, Takatori A, Ogura A, Kohashi Okay, Souzaki R, Kinoshita Y, Taguchi T, Hossain MS, Ohira M, Nakamura Y, Nakagawara A
In neuroblastoma (NB), probably the most widespread paediatric strong tumours, activation of anaplastic lymphoma kinase (ALK) is usually related to poor outcomes. Though genetic research have recognized copy quantity alteration and nonsynonymous mutations of ALK, the regulatory mechanism of ALK signalling at protein ranges is basically elusive. Neuronal leucine-rich repeat 1 (NLRR1) is a kind 1 transmembrane protein that’s extremely expressed in unfavourable NB and doubtlessly influences receptor tyrosine kinase signalling. Right here, we confirmed that NLRR1 and ALK exhibited a mutually unique expression sample in major NB tissues by immunohistochemistry. Furthermore, dorsal root ganglia of Nlrr1+/+ and Nlrr1-/- mice displayed the other expression patterns of Nlrr1 and Alk. Of curiosity, NLRR1 bodily interacted with ALK in vitro by way of its extracellular area. Notably, the NLRR1 ectodomain impaired ALK phosphorylation and proliferation of ALK-mutated NB cells. A newly recognized cleavage of the NLRR1 ectodomain additionally supported NLRR1-mediated ALK sign regulation in trans. Thus, we conclude that NLRR1 seems to be an extracellular destructive regulator of ALK signalling in NB and neuronal improvement. Our findings could also be helpful to understand NB heterogeneity and to develop a novel remedy in opposition to unfavourable NB.
PMID: 27604320 [PubMed – indexed for MEDLINE]