Open AccessAxl acts as a tumor suppressor by regulating LIGHT expression in T lymphoma
Author(s) -
Eun-Hee Lee,
EunMi Kim,
Kon-Young Ji,
A-Reum Park,
Hyungsub Choi,
Hwa-Youn Lee,
Su-Man Kim,
Byung Yeoup Chung,
ChulHong Park,
Hyo Jin Choi,
YoungHyeh Ko,
HyoungWoo Bai,
HyungSik Kang
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.15830
Subject(s) - cytotoxic t cell , jurkat cells , cancer research , tumor microenvironment , biology , downregulation and upregulation , axl receptor tyrosine kinase , natural killer cell , microbiology and biotechnology , receptor tyrosine kinase , t cell , immune system , immunology , signal transduction , jak stat signaling pathway , biochemistry , gene , in vitro
Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1. The lytic activity of cytotoxic T lymphocytes and natural killer cells was enhanced by EL4-Axl cells. In addition, tumor volume and growth were markedly reduced due to enhanced apoptotic cell death in EL4-Axl tumor-bearing mice as compared to control mice. We also observed upregulated expression of CCL5 and its receptor, CCR5, and enhanced intratumoral infiltration of cytotoxic T lymphocytes and natural killer cells in EL4-Axl-bearing mice as compared to mock controls. These data strongly suggested that Axl exerts novel tumor suppressor effects by inducing upregulation of LIGHT in the tumor microenvironment of T lymphoma.