Oncogene, 2019-05, Vol.38 (20), p.3903-3918
2019
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- Autor(en) / Beteiligte
- Titel
- RUNX3 enhances TRAIL-induced apoptosis by upregulating DR5 in colorectal cancer
- Ist Teil von
- Oncogene, 2019-05, Vol.38 (20), p.3903-3918
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- RUNX3 is frequently inactivated by DNA hypermethylation in numerous cancers. Here, we show that RUNX3 has an important role in modulating apoptosis in immediate response to tumor necrosis factor-related apoptosis-including ligand (TRAIL). Importantly, no combined effect of TRAIL and RUNX3 was observed in non-cancerous cells. We investigated the expression of the death receptors (DRs) DR4 and DR5, which are related to TRAIL resistance. Overexpression of RUNX3 increased DR5 expression via induction of the reactive oxygen species (ROS)-endoplasmic reticulum (ER) stress-effector CHOP. Reduction of DR5 markedly decreased apoptosis enhanced by the combined therapy of TRAIL and RUNX3. Interestingly, RUNX3 induced reactive oxygen species production by inhibiting SOD3 transcription via binding to the Superoxide dismutase 3 (SOD3) promoter. Additionally, the combined effect of TRAIL and RUNX3 decreased tumor growth in xenograft models. Our results demonstrate a direct role for RUNX3 in TRAIL-induced apoptosis via activation of DR5 and provide further support for RUNX3 as an anti-tumor.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/s41388-019-0693-xTitel-ID: cdi_proquest_miscellaneous_2179448768
- Format
- –
- Schlagworte
- 13/109, 13/2, 13/31, 38, 38/1, 42, 631/67/1059/2326, 631/67/2195, 82, 82/51, 96, 96/95, Apoptosis, Apoptosis - physiology, Cancer genetics, Cell Biology, Colorectal cancer, Colorectal carcinoma, Colorectal Neoplasms - genetics, Colorectal Neoplasms - pathology, Core Binding Factor Alpha 3 Subunit - genetics, Core Binding Factor Alpha 3 Subunit - metabolism, Death receptors, DNA, Endoplasmic reticulum, Endoplasmic Reticulum Stress, Female, Genetic aspects, HT29 Cells, Human Genetics, Humans, Internal Medicine, Male, Medicine, Medicine & Public Health, Necrosis, Oncology, Reactive oxygen species, Reactive Oxygen Species - metabolism, Receptors, TNF-Related Apoptosis-Inducing Ligand - genetics, Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism, Risk factors, Runx3 protein, Superoxide dismutase, Superoxide Dismutase - metabolism, Superoxides, TNF-Related Apoptosis-Inducing Ligand - genetics, TNF-Related Apoptosis-Inducing Ligand - metabolism, TRAIL protein, Transcription, Transcription Factor CHOP - metabolism, Tumor necrosis factor, Tumors, Up-Regulation, Xenografts