单位：[1]Moores Cancer Center, University of California San Diego,La Jolla, CA, USA[2]Department of Otolaryngology—Head and Neck Surgery, BeijingFriendship Hospital, Capital Medical University, Beijing, China首都医科大学附属北京友谊医院[3]Department of Otolaryngology—Head and Neck Surgery,Johns Hopkins Medical Institutions, Baltimore, MD, USA[4]Division of Oncology Biostatistics, Department of Oncology,Johns Hopkins Medical Institutions, Baltimore, MD, USA[5]Laboratory of Systems Biology and Computational Genetics,Vavilov Institute of General Genetics, Russian Academy ofSciences, Moscow, Russia[6]Department of Medicine, University of California San Diego,La Jolla, CA, USA[7]Cancer Biology and Immunotherapies group, Sanford Research,Sioux Falls, SD, USA[8]Division of Otolaryngology—Head and Neck Surgery,Department of Surgery, University of California San Diego,La Jolla, CA, USA
The dominant paradigm for HPV carcinogenesis includes integration into the host genome followed by expression of E6 and E7 (E6/E7). We explored an alternative carcinogenic pathway characterized by episomal E2, E4, and E5 (E2/E4/E5) expression. Half of HPV positive cervical and pharyngeal cancers comprised a subtype with increase in expression of E2/E4/E5, as well as association with lack of integration into the host genome. Models of the E2/E4/E5 carcinogenesis show p53 dependent enhanced proliferation in vitro, as well as increased susceptibility to induction of cancer in vivo. Whole genomic expression analysis of the E2/E4/E5 pharyngeal cancer subtype is defined by activation of the fibroblast growth factor receptor (FGFR) pathway and this subtype is susceptible to combination FGFR and mTOR inhibition, with implications for targeted therapy.
基金：
National Institute of Dental and Craniofacial ResearchUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR); NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [P30 CA006973, R01 DE023347]; UC San Diego Clinical and Translational Research Institute Grant [UL1TR001442]; Russian Basic Research Foundation (RBRF) [17-00-00208]; Russian Academy of Sciences Project [0112-2019-0001]
第一作者单位：[1]Moores Cancer Center, University of California San Diego,La Jolla, CA, USA[2]Department of Otolaryngology—Head and Neck Surgery, BeijingFriendship Hospital, Capital Medical University, Beijing, China
通讯作者：
通讯机构：[1]Moores Cancer Center, University of California San Diego,La Jolla, CA, USA[8]Division of Otolaryngology—Head and Neck Surgery,Department of Surgery, University of California San Diego,La Jolla, CA, USA
推荐引用方式(GB/T 7714)：
Ren Shuling,Gaykalova Daria A.,Guo Theresa,et al.HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers[J].ONCOGENE.2020,39(40):6327-6339.doi:10.1038/s41388-020-01431-8.
APA：
Ren, Shuling,Gaykalova, Daria A.,Guo, Theresa,Favorov, Alexander, V,Fertig, Elana J....&Califano, Joseph A..(2020).HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers.ONCOGENE,39,(40)
MLA：
Ren, Shuling,et al."HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers".ONCOGENE 39..40(2020):6327-6339
医学