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B cell linker protein (BLNK) is a regulator of Met receptor signaling and trafficking in non-small cell lung cancer.

Authors :
Pathmanathan S
Yao Z
Coelho P
Valla R
Drecun L
Benz C
Snider J
Saraon P
Grozavu I
Kotlyar M
Jurisica I
Park M
Stagljar I
Source :
IScience [iScience] 2022 Oct 20; Vol. 25 (11), pp. 105419. Date of Electronic Publication: 2022 Oct 20 (Print Publication: 2022).
Publication Year :
2022

Abstract

Met is an oncogene aberrantly activated in multiple cancers. Therefore, to better understand Met biology and its role in disease we applied the Ma mmalian M embrane T wo- H ybrid (MaMTH) to generate a targeted interactome map of its interactions with human SH2/PTB-domain-containing proteins. We identified thirty interaction partners, including sixteen that were previously unreported. Non-small cell lung cancer (NSCLC)-focused functional characterization of a Met-interacting protein, BLNK, revealed that BLNK is a positive regulator of Met signaling, and modulates localization, including ligand-dependent trafficking of Met in NSCLC cell lines. Furthermore, the interaction between Met and GRB2 is increased in the presence of BLNK, and the constitutive interaction between BLNK and GRB2 is increased in the presence of active Met. Tumor phenotypical assays uncovered roles for BLNK in anchorage-independent growth and chemotaxis of NSCLC cell lines. Cumulatively, this study provides a Met-interactome and delineates a role for BLNK in regulating Met biology in NSCLC context.<br />Competing Interests: Authors declare no competing financial interests.<br /> (© 2022 The Authors.)

Details

Language :
English
ISSN :
2589-0042
Volume :
25
Issue :
11
Database :
MEDLINE
Journal :
IScience
Publication Type :
Academic Journal
Accession number :
36388990
Full Text :
https://doi.org/10.1016/j.isci.2022.105419