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Novel Insights Into Cellular Changes in HPV8-E7 Positive Keratinocytes: A Transcriptomic and Proteomic Analysis
Matthias Kirschberg1, Adnan Shahzad Syed1, Hanife Güler Dönmez1,2
1Medical Faculty and University Hospital Cologne, Institute of Virology, University of Cologne, Cologne, Germany.
Frontiers in Microbiology
|September 23, 2021
Summary
Human papillomavirus type 8 (HPV8) drives skin cancer by altering keratinocyte invasion. HPV8 E7 oncoprotein activates Fyn and Lyn kinases, impacting DNA repair and cell structure for tumor growth.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Human papillomavirus type 8 (HPV8) is linked to non-melanoma skin cancer.
- The viral E7 oncoprotein mediates keratinocyte invasion, influenced by fibronectin.
Purpose of the Study:
- To characterize gene and protein alterations in HPV8 E7-expressing keratinocytes.
- To identify key cellular targets of HPV8 E7.
Main Methods:
- Gene expression analysis (GADD34, GDF15).
- Identification of fibronectin-associated factors (Src kinase family: Fyn, Lyn).
- Phospho-proteomics to analyze protein phosphorylation changes.
Main Results:
- HPV8 E7 strongly activates GADD34 and GDF15 gene expression.
- Fyn and Lyn kinases are aberrantly activated by HPV8 E7.
- E7 deregulates phosphorylation of nuclear proteins involved in DNA repair and replication, many of which are Fyn/Lyn targets.
Conclusions:
- HPV8 E7 impacts signaling cascades in keratinocytes via fibronectin.
- These alterations are crucial for skin tumorigenesis.
- Findings may inform novel therapeutic strategies for beta-HPV-mediated cancers.
