Inhibition of the mevalonate pathway enhances cancer cell oncolysis mediated by M1 virus
| العنوان: | Inhibition of the mevalonate pathway enhances cancer cell oncolysis mediated by M1 virus |
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| المؤلفون: | Yaqian Tan, Li Guo, Yuan Lin, Chuntao Li, Ying Liu, Songmin He, Jing Cai, Xincheng Liu, Zhang Haipeng, Guangmei Yan, Yaya Yu, Xingwen Su, Jiankai Liang, Jun Hu, Xiaoke Zheng, Pengxin Qiu, Wenbo Zhu, Kai Li, Cheng Hu, Xiao Xiao |
| المصدر: | Nature Communications, Vol 9, Iss 1, Pp 1-12 (2018) Nature Communications |
| بيانات النشر: | Nature Publishing Group, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cell Survival, Science, viruses, Protein Prenylation, Down-Regulation, Mevalonic Acid, General Physics and Astronomy, Virus Replication, Article, General Biochemistry, Genetics and Molecular Biology, Virus, Mice, 03 medical and health sciences, Cell Line, Tumor, medicine, Animals, Farnesyltranstransferase, Humans, RNA, Small Interfering, lcsh:Science, Oncolytic Virotherapy, Mice, Inbred BALB C, Multidisciplinary, Chemistry, Farnesyl Transferase Inhibitor, Cancer, General Chemistry, HCT116 Cells, medicine.disease, Oncolytic virus, Oncolytic Viruses, Cholesterol, 030104 developmental biology, rab GTP-Binding Proteins, Gene Knockdown Techniques, Cancer cell, Cancer research, Protein farnesylation, Protein prenylation, Female, RNA Interference, lcsh:Q, Mevalonate pathway, Neoplasm Transplantation |
| الوصف: | Oncolytic virus is an attractive anticancer agent that selectively lyses cancer through targeting cancer cells rather than normal cells. Although M1 virus is effective against several cancer types, certain cancer cells present low sensitivity to it. Here we identified that most of the components in the cholesterol biosynthesis pathway are downregulated after M1 virus infection. Further functional studies illustrate that mevalonate/protein farnesylation/ras homolog family member Q (RHOQ) axis inhibits M1 virus replication. Further transcriptome analysis shows that RHOQ knockdown obviously suppresses Rab GTPase and ATP-mediated membrane transporter system, which may mediate the antiviral effect of RHOQ. Based on this, inhibition of the above pathway significantly enhances the anticancer potency of M1 virus in vitro, in vivo, and ex vivo. Our research provides an intriguing strategy for the rational combination of M1 virus with farnesyl transferase inhibitors to enhance therapeutic efficacy. Oncolytic viruses selectively kill tumour cells and induce anti-tumour immunity. Here, the AUs demonstrate the anti-viral effect of the mevalonate pathway on oncolytic virus M1 in refractory cancer cells and provide evidence for a combination strategy of targeting the mevalonate pathway for potentiating oncolytic virus therapy. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6efa145f38fe1d16c3ef25e717eb9eb9Test http://link.springer.com/article/10.1038/s41467-018-03913-6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6efa145f38fe1d16c3ef25e717eb9eb9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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