RAE1 ligands for the NKG2D receptor are regulated by STING-dependent DNA sensor pathways in lymphoma
Autor: | Li F. M. Tang, John Ludovic Croxford, Yu J. Shen, Stephan Gasser, Nina Le Bert, Shizuo Akira, Christine Xing’Er Koo, Samantha S.W. Ho, Gordon Minru Xiong, Adeline R. Lam, David H. Raulet, Ken Ishii |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Cancer Research
Nucleocytoplasmic Transport Proteins Lymphoma DNA damage Oncology and Carcinogenesis Retinoic acid Mice Transgenic Biology Protein Serine-Threonine Kinases Inbred C57BL Ligands Transfection Transgenic Article Cell Line chemistry.chemical_compound Mice Nuclear Matrix-Associated Proteins Cell Line Tumor Killer Cells Animals Oncology & Carcinogenesis Phosphorylation Immunologic Surveillance Tumor Effector Membrane Proteins DNA DNA Neoplasm Protein-Serine-Threonine Kinases NKG2D Cell biology Up-Regulation Immunosurveillance Killer Cells Natural Mice Inbred C57BL Oncology chemistry Cell culture NK Cell Lectin-Like Receptor Subfamily K Cancer cell Natural Neoplasm Interferon Regulatory Factor-3 DNA Damage |
Zdroj: | Lam, AR; Bert, NL; Ho, SSW; Shen, YJ; Tang, MLF; Xiong, GM; et al.(2014). RAE1 ligands for the NKG2D receptor are regulated by STING-dependent DNA sensor pathways in lymphoma. Cancer Research, 74(8), 2193-2203. doi: 10.1158/0008-5472.CAN-13-1703. UC Berkeley: Retrieved from: http://www.escholarship.org/uc/item/7n26z2hx Cancer research, vol 74, iss 8 |
DOI: | 10.1158/0008-5472.CAN-13-1703. |
Popis: | The immunoreceptor NKG2D originally identified in natural killer (NK) cells recognizes ligands that are upregulated on tumor cells. Expression of NKG2D ligands (NKG2DL) is induced by the DNA damage response (DDR), which is often activated constitutively in cancer cells, revealing them to NK cells as a mechanism of immunosurveillance. Here, we report that the induction of retinoic acid early transcript 1 (RAE1) ligands for NKG2D by the DDR relies on a STING-dependent DNA sensor pathway involving the effector molecules TBK1 and IRF3. Cytosolic DNA was detected in lymphoma cell lines that express RAE1 and its occurrence required activation of the DDR. Transfection of DNA into ligand-negative cells was sufficient to induce RAE1 expression. Irf3+/−;Eμ-Myc mice expressed lower levels of RAE1 on tumor cells and showed a reduced survival rate compared with Irf3+/+;Eμ-Myc mice. Taken together, our results suggest that genomic damage in tumor cells leads to activation of STING-dependent DNA sensor pathways, thereby activating RAE1 and enabling tumor immunosurveillance. Cancer Res; 74(8); 2193–203. ©2014 AACR. |
Databáze: | OpenAIRE |
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