HPV-E6 protein enriches the CD55(+) population in cervical cancer cells promoting radio-resistance and cancer aggressiveness

Abstract

Accumulating evidence indicates that the human papilloma virus (HPV) E6 protein plays a crucial role in the development of cervical cancer. Sub-populations of cells that reside within tumors are responsible for tumor resistance to cancer therapy and recurrence. However, the identity of such cells residing in cervical cancer and their relationship with the HPV-E6 protein have not been identified. Here, we isolated sphere-forming cells, which exhibited self-renewal ability, from primary cervical tumors. Gene expression profiling revealed that CD55 was upregulated in primary cervical cancer sphere cells. Flow cytometric analysis detected abundant CD55(+) populations among a panel of HPV-positive cervical cancer cell lines, while only few CD55(+) cells were found in HPV-negative cervical cancer and normal cervical epithelial cell lines. The isolated CD55(+) sub-population from the C33A cell line exhibited significant sphere-forming ability and enhanced tumorigenicity, cell migration and radio-resistance. In contrast, the suppression of CD55 in HPV-positive CaSki cells inhibited tumorigenicity both in vitro and in vivo and sensitized cells to irradiation treatment. In addition, ectopic expression of HPV-E6 in HPV-negative cervical cancer cells dramatically enriched the CD55(+) sub-population. CRISPR/Cas9 knockout of the CD55 gene in an HPV-E6-overexpressing stable clone abolished the tumorigenic properties exerted by HPV-E6. Taken together, our data suggest that HPV-E6 protein expression enriches the CD55(+) population, which contributes to tumorigenicity and radio-resistance in cervical cancer cells. Targeting CD55 via CRISPR/Cas9 may represent a novel avenue for developing new strategies and effective therapies for the treatment of cervical cancer.

from # All Medicine by Alexandros G. Sfakianakis via alkiviadis.1961 on Inoreader http://ift.tt/2fsRQ57