Secreted human glycyl-tRNA synthetase implicated in defense against ERK-activated tumorigenesis

Cited 95 time in scopus
Metadata Downloads
Title
Secreted human glycyl-tRNA synthetase implicated in defense against ERK-activated tumorigenesis
Author(s)
M C Park; T Kang; D Jin; J M Han; S B Kim; Y J Park; K Cho; Young Woo Park; M Guo; W He; X L Yang; P Schimmel; S Kim
Bibliographic Citation
Proceedings of National Academy of Sciences of United States of America, vol. 109, no. 11, pp. E640-E647
Publication Year
2012
Abstract
Although adaptive systems of immunity against tumor initiation and destruction are well investigated, less understood is the role, if any, of endogenous factors that have conventional functions. Here we show that glycyl-tRNA synthetase (GRS), an essential component of the translation apparatus, circulates in serum and can be secreted from macrophages in response to Fas ligand that is released from tumor cells. Through cadherin (CDH)6 (K-cadherin), GRS bound to different ERK-activated tumor cells, and released phosphatase 2A (PP2A) from CDH6. The activated PP2A then suppressed ERK signaling through dephosphorylation of ERK and induced apoptosis. These activities were inhibited by blocking GRS with a soluble fragment of CDH6. With in vivo administration of GRS, growth of tumors with a high level of CDH6 and ERK activation were strongly suppressed. Our results implicate a conventional cytoplasmic enzyme in translation as an intrinsic component of the defense against ERK-activated tumor formation.
Keyword
Cancer microenvironmentCytokineImmune surveillanceProapoptotic effect
ISSN
0027-8424
Publisher
Natl Acad Sciences
DOI
http://dx.doi.org/10.1073/pnas.1200194109
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.