HPV Type 16 Infection Switches Keratinocytes from Apoptotic to Proliferative Fate Under TWEAK/Fn14 Interaction

Overview

Journal J Invest Dermatol

Publisher Elsevier

Specialty Dermatology

Date 2015 May 29

PMID 26016896

Citations 13

Authors

Hong Cheng

Na Zhan

Dong Ding

Xiaoming Liu

Xiaoyan Zou

Ke Li

Yumin Xia

Affiliations

Soon will be listed here.

Abstract

Previously, tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) had been known to be an inducer of apoptosis of keratinocytes by engaging the Fn14 receptor. However, the high-risk human papillomavirus (HPV) infection confers a proliferation advantage on keratinocytes that may consequently harbor tumorigenicity. This study was designed to investigate the cross-talk in keratinocytes between TWEAK/Fn14 signaling and HPV type 16 infection, which may cooperate in regulating cell-cycle progression. TWEAK and Fn14 expression was determined in anogenital warts and normal skin. Both primary keratinocytes and HaCaT cells were transfected with HPV16 E6/E7 genes. The results showed that Fn14 is highly expressed upon HPV16 transfection and accompanied by an increase in Ras GTPase activity and TNF-receptor-associated factor 2 (TRAF2) expression. Moreover, the E6/E7-transfected keratinocytes exhibit a shift of TNF receptor profile from type 1 to type 2 and weakened apoptotic response to TNF-α stimuli, when compared with the normal control. Surprisingly, significant increase in proliferation but not apoptosis was seen in E6/E7-positive keratinocytes, as TWEAK was additionally supplemented. In conclusion, the HPV16 infection in keratinocytes causes a switch of apoptotic to proliferative fate under TWEAK/Fn14 interaction, possibly by favoring Ras and TRAF2 activation and modulating TNF receptor expression.

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