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HPV16 E6/E7 upregulates HIF-2α and VEGF by inhibiting LKB1 in lung cancer cells.
- Source :
-
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine [Tumour Biol] 2017 Jul; Vol. 39 (7), pp. 1010428317717137. - Publication Year :
- 2017
-
Abstract
- Long-term persistent infection of HPV16 E6/E7 is frequently associated with lung cancers, especially in non-smokers and in Asians. However, molecular mechanisms of HPV16 E6/E7 induction of lung cancer are not fully understood. Using bi-directional genetic manipulation and four well-established lung cancer cell lines, we showed HPV16 E6/E7 downregulated expression of liver kinase B1 at both protein and messenger RNA levels; liver kinase B1 downregulated hypoxia-inducible factor 2α at protein level but not at messenger RNA level, and hypoxia-inducible factor 2α upregulated vascular endothelial growth factor at both protein and messenger RNA levels. This is the first study to show hypoxia-inducible factor 2α as a downstream effector of liver kinase B1 in lung cancer cells. Our results indicate that HPV16 E6/E7 indirectly upregulated the expression of vascular endothelial growth factor by inhibition of liver kinase B1 expression and upregulation of hypoxia-inducible factor 2α expression, thus propose a human papillomavirus-liver kinase B1-hypoxia-inducible factor 2α-vascular endothelial growth factor axis for the tumorigenesis of lung cancer. Our study also provides new evidence to support the critical role of liver kinase B1 in the pathogenesis of human papillomavirus-related lung cancer and suggests novel therapeutic targets.
- Subjects :
- AMP-Activated Protein Kinase Kinases
Basic Helix-Loop-Helix Transcription Factors genetics
Cell Line, Tumor
Gene Expression Regulation, Neoplastic genetics
Human papillomavirus 16 pathogenicity
Humans
Lung Neoplasms pathology
Lung Neoplasms virology
Protein Serine-Threonine Kinases genetics
Transcriptional Activation genetics
Vascular Endothelial Growth Factor A genetics
Basic Helix-Loop-Helix Transcription Factors biosynthesis
Human papillomavirus 16 genetics
Lung Neoplasms genetics
Oncogene Proteins, Viral genetics
Papillomavirus E7 Proteins genetics
Protein Serine-Threonine Kinases biosynthesis
Repressor Proteins genetics
Vascular Endothelial Growth Factor A biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0380
- Volume :
- 39
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 28720067
- Full Text :
- https://doi.org/10.1177/1010428317717137