HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers.

Abstract:

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

Ren S,Gaykalova DA,Guo T,Favorov AV,Fertig EJ,Tamayo P,Callejas-Valera JL,Allevato M,Gilardi M,Santos J,Fukusumi T,Sakai A,Ando M,Sadat S,Liu C,Xu G,Fisch KM,Wang Z,Molinolo AA,Gutkind JS,Ideker T,Koch WM,Cali

doi

10.1038/s41388-020-01431-8

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

6327-6339

issue

40

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-020-01431-8

journal_volume

39

pub_type

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