期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 11, 页码 E640-E647出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1200194109
关键词
cytokine; proapoptotic effect; immune surveillance; cancer microenvironment
资金
- National Research Foundation [NRF-M1AXA002-2011-0028417, R17-2007-020-01000-0]
- Ministry of Education, Science, and Technology of Korea
- National Institutes of Health [GM15539, 23562, GM088278]
- National Foundation for Cancer Research
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.
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