Abstract 5341: HPV16 E6 oncoprotein modulates the DPPIV/CD26 in primary keratinocytes

Abstract

Abstract Cervical cancer is related to the persistent infection by high-risk human papillomavirus (HPV) subtypes, such as types 16 and 18. The E6 and E7 oncoproteins significantly contribute to the carcinogenic potential of high-risk HPV, through the degradation of p53 and pRb, respectively. The exoprotease dipeptidyl peptidase IV (DPPIV) also known as CD26, is a multifunctional protein involved in several processes related to cancer. DPPIV/CD26 has an intrinsic peptidase activity, able to degrade some bioactive peptides and chemokines, thereby regulating cell migration, proliferation and survival. It has been reported that the reduction in DPPIV/CD26 expression is associated with tumor progression in different types of cancer. Moreover, studies in cervical cancer samples and cell lines point to a reduction in the expression of this protein. However, there are no studies addressing the relationship between HPV infection and DPPIV/CD26 expression. We analyzed the influence of HPV oncoproteins on DPPIV/CD26 expression in human keratinocyte transduced with E6, E7 and E6E7. We observed that HPV16 E6 expression is associated to a reduction in DPPIV/CD26 expression at mRNA and protein levels, whereas HPV16 E7 does not affect DPPIV/CD26 expression. HPV16 E6E7 co-expression leads to a reduction in DPPIV/CD26 expression similar to that found in E6 transduced cells. In addition, we note a more pronounced reduction in DPPIV/CD26 expression in immortalized cells expressing E6E7. Furthermore, keratinocytes expressing HPV16 E6 mutant sequence and HPV11 E6, that do not bind to E6AP and do not degrade p53, have no effect on DPPIV/CD26 expression. Our results suggest that the HPV16 E6 oncoprotein can downregulates DPPIV/CD26. In addition, preliminary results suggest that modulation of DPPIV/CD6 mediated by E6 can be dependent on degradation of p53, since HPV16 E6 mutant and low-risk HPV E6 were not able to affect CD26 expression. Furthermore, the process of cell immortalization also appears to be related to the reduction of DPPIV/CD26 expression. Therefore, these results indicate that HPV oncoproteins promote imbalance DPPIV/CD26 expression which may be relate to cervical carcinogenesis. Citation Format: Aline Beckenkamp, Bruna Prati, Silvya Stuchi Maria-Engler, Guido Lenz, Diogo André Pilger, Enrique Mario Pierulivo, Andréia Buffon. HPV16 E6 oncoprotein modulates the DPPIV/CD26 in primary keratinocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5341. doi:10.1158/1538-7445.AM2017-5341