Advanced

Bruton’s tyrosine kinase potentiates ALK signaling and serves as a potential therapeutic target of neuroblastoma

Li, Tianfeng; Deng, Yi; Shi, Yu; Tian, Ruijun; Chen, Yonglong; Zou, Lin; Kazi, Julhash U. LU ; Rönnstrand, Lars LU ; Feng, Bo and Chan, Sun On, et al. (2018) In Oncogene
Abstract

Aberrant activation of anaplastic lymphoma kinase (ALK) can cause sporadic and familial neuroblastoma. Using a proteomics approach, we identified Bruton’s tyrosine kinase (BTK) as a novel ALK interaction partner, and the physical interaction was confirmed by co-immunoprecipitation. BTK is expressed in neuroblastoma cell lines and tumor tissues. Its high expression correlates with poor relapse-free survival probability of neuroblastoma patients. Mechanistically, we demonstrated that BTK potentiates ALK-mediated signaling in neuroblastoma, and increases ALK stability by reducing ALK ubiquitination. Both ALKWT and ALKF1174L can induce BTK phosphorylation and higher capacity of ALKF1174L is observed.... (More)

Aberrant activation of anaplastic lymphoma kinase (ALK) can cause sporadic and familial neuroblastoma. Using a proteomics approach, we identified Bruton’s tyrosine kinase (BTK) as a novel ALK interaction partner, and the physical interaction was confirmed by co-immunoprecipitation. BTK is expressed in neuroblastoma cell lines and tumor tissues. Its high expression correlates with poor relapse-free survival probability of neuroblastoma patients. Mechanistically, we demonstrated that BTK potentiates ALK-mediated signaling in neuroblastoma, and increases ALK stability by reducing ALK ubiquitination. Both ALKWT and ALKF1174L can induce BTK phosphorylation and higher capacity of ALKF1174L is observed. Furthermore, the BTK inhibitor ibrutinib can effectively inhibit the growth of neuroblastoma xenograft in nude mice, and the combination of ibrutinib and the ALK inhibitor crizotinib further enhances the inhibition. Our study provides strong rationale for clinical trial of ALK-positive neuroblastoma using ibrutinib or the combination of ibrutinib and ALK inhibitors.

(Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
epub
subject
in
Oncogene
pages
15 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85049962646
ISSN
0950-9232
DOI
10.1038/s41388-018-0397-7
language
English
LU publication?
yes
id
a30a1584-8599-4afc-9633-5de1a9d21a0c
date added to LUP
2018-08-01 13:31:48
date last changed
2018-08-30 10:30:10
@article{a30a1584-8599-4afc-9633-5de1a9d21a0c,
  abstract     = {<p>Aberrant activation of anaplastic lymphoma kinase (ALK) can cause sporadic and familial neuroblastoma. Using a proteomics approach, we identified Bruton’s tyrosine kinase (BTK) as a novel ALK interaction partner, and the physical interaction was confirmed by co-immunoprecipitation. BTK is expressed in neuroblastoma cell lines and tumor tissues. Its high expression correlates with poor relapse-free survival probability of neuroblastoma patients. Mechanistically, we demonstrated that BTK potentiates ALK-mediated signaling in neuroblastoma, and increases ALK stability by reducing ALK ubiquitination. Both ALK<sup>WT</sup> and ALK<sup>F1174L</sup> can induce BTK phosphorylation and higher capacity of ALK<sup>F1174L</sup> is observed. Furthermore, the BTK inhibitor ibrutinib can effectively inhibit the growth of neuroblastoma xenograft in nude mice, and the combination of ibrutinib and the ALK inhibitor crizotinib further enhances the inhibition. Our study provides strong rationale for clinical trial of ALK-positive neuroblastoma using ibrutinib or the combination of ibrutinib and ALK inhibitors.</p>},
  author       = {Li, Tianfeng and Deng, Yi and Shi, Yu and Tian, Ruijun and Chen, Yonglong and Zou, Lin and Kazi, Julhash U. and Rönnstrand, Lars and Feng, Bo and Chan, Sun On and Chan, Wai Yee and Sun, Jianmin and Zhao, Hui},
  issn         = {0950-9232},
  language     = {eng},
  month        = {07},
  pages        = {15},
  publisher    = {Nature Publishing Group},
  series       = {Oncogene},
  title        = {Bruton’s tyrosine kinase potentiates ALK signaling and serves as a potential therapeutic target of neuroblastoma},
  url          = {http://dx.doi.org/10.1038/s41388-018-0397-7},
  year         = {2018},
}