HPV E2, E4, E5 drive alternative carcinogenic pathways in HPV positive cancers.
Animals
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Carcinogenesis
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ genetics
Datasets as Topic
Disease Models, Animal
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Gene Expression Regulation, Viral
/ drug effects
Host-Pathogen Interactions
/ genetics
Human papillomavirus 16
/ genetics
Humans
Mice
Mice, Transgenic
Oncogene Proteins, Viral
/ genetics
Papillomavirus Infections
/ drug therapy
Pharyngeal Neoplasms
/ drug therapy
Primary Cell Culture
Receptors, Fibroblast Growth Factor
/ antagonists & inhibitors
Signal Transduction
/ drug effects
Squamous Cell Carcinoma of Head and Neck
/ drug therapy
TOR Serine-Threonine Kinases
/ antagonists & inhibitors
Tumor Suppressor Protein p53
/ metabolism
Uterine Cervical Neoplasms
/ drug therapy
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
19
02
2020
accepted:
13
08
2020
revised:
19
07
2020
pubmed:
28
8
2020
medline:
15
12
2020
entrez:
28
8
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32848210
doi: 10.1038/s41388-020-01431-8
pii: 10.1038/s41388-020-01431-8
pmc: PMC7529583
mid: NIHMS1620247
doi:
Substances chimiques
Oncogene Proteins, Viral
0
Receptors, Fibroblast Growth Factor
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6327-6339Subventions
Organisme : NCI NIH HHS
ID : U24 CA194107
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA220341
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA177669
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE023347
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217885
Pays : United States
Organisme : NIDCR NIH HHS
ID : RC2 DE020789
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA248457
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001442
Pays : United States
Organisme : NIDCR NIH HHS
ID : RC1 DE020324
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE027809
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG009285
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE026870
Pays : United States
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