| Author/Editor | Chen, Jianzhou; Markelc, Boštjan; Kaeppler, Jakob; Ogundipe, Vivian M. L.; Cao, Yunhong; McKenna, Gillies W.; Muschel, Ruth J. | |
| Title | STING-dependent interferon-[lambda]1 induction in HT29 cells, a human colorectal cancer cell line, after gamma-radiation | |
| Type | članek | |
| Vol. and No. | Letnik 101, št. 1 | |
| Publication year | 2018 | |
| Volume | str. 97-106 | |
| ISSN | 0360-3016 - International journal of radiation oncology, biology, physics | |
| Language | eng | |
| Abstract | Purpose To investigate the induction of type III interferons (IFNs) in human cancer cells by gamma-rays. Methods and Materials Type III IFN expression in human cancer cell lines after gamma-ray irradiation in vitro was assessed by reverse transcription%quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Signaling pathways mediating type III IFN induction were examined by a variety of means, including immunoblotting, flow cytometry, confocal imaging, and reverse transcription%quantitative polymerase chain reaction. Key mediators in these pathways were further explored and validated using gene CRISPR knockout or short hairpin RNA knockdown. Results Exposure to gamma-rays directly induced type III IFNs (mainly IFNL1) in human cancer cell lines in dose- and time-dependent fashions. The induction of IFNL1 was primarily mediated by the cytosolic DNA sensors%STING%TBK1%IRF1 signaling axis, with a lesser contribution from the nuclear factor kappa b signaling in HT29 cells. In addition, type III IFN signaling through its receptors serves as a positive feedback loop, further enhancing IFN expression via up-regulation of the kinases in the STING%TBK1 signaling axis. Conclusions Our results suggest that IFNL1 can be up-regulated in human cancer cell lines after gamma-ray treatment. In HT29 cells this induction occurs via the STING pathway, adding another layer of complexity to the understanding of radiation-induced antitumor immunity, and may provide novel insights into IFN-based cancer treatment. | |
| Keywords | radioterapija rak debelega črevesa in danke interferoni radiotherapy colorectal cancer interferons |