HPV16 E6 oncoprotein increases cell adhesion in human keratinocytes

Area of Science:

• Cell Biology
• Virology
• Oncology

Background:

• The E6 oncoprotein of human papillomavirus (HPV) 16 is known to reduce apoptosis in primary human keratinocytes (PHKs).
• Increased cell adhesion has been hypothesized as a potential mechanism underlying this reduced apoptosis.

Purpose of the Study:

• To investigate whether HPV16 E6 expression increases cell adhesion.
• To determine the role of the p53 targeting region of E6 in mediating this effect.
• To explore the molecular pathways involved in E6-mediated cell adhesion.

Main Methods:

• Cell adhesion assays were performed using PHKs, HaCaT, and 293T cells seeded on poly(HEME)-coated dishes.
• The E6 gene was introduced via retroviral infection or DNA transfection.
• HPV16 E6 mutants were analyzed for their effect on cell adhesion in 293T cells.
• Tyrosine kinase inhibition assays using bombesin were conducted.

Main Results:

• Expression of HPV16 E6 significantly increased the proportion of attached cells across all cell types tested.
• Mutational analysis revealed that the p53-binding domain of E6 is dispensable for enhancing cell adhesion.
• Inhibition of tyrosine kinases by bombesin suggests E6 may employ alternative signaling pathways to modulate cell adhesion.

Conclusions:

• HPV16 E6 expression enhances cell adhesion in human keratinocytes and other cell lines.
• The mechanism by which E6 increases cell adhesion does not rely on its ability to target p53.
• Alternative signaling pathways, potentially involving tyrosine kinases, are likely responsible for E6-mediated cell adhesion modulation.