PMID- 26016896
OWN - NLM
STAT- MEDLINE
DCOM- 20151214
LR  - 20181113
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Linking)
VI  - 135
IP  - 10
DP  - 2015 Oct
TI  - HPV Type 16 Infection Switches Keratinocytes from Apoptotic to Proliferative Fate 
      under TWEAK/Fn14 Interaction.
PG  - 2427-2436
LID - S0022-202X(15)41807-X [pii]
LID - 10.1038/jid.2015.201 [doi]
AB  - 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-alpha 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.
FAU - Cheng, Hong
AU  - Cheng H
AD  - Department of Dermatology, The Second Affiliated Hospital, School of Medicine, 
      Xi'an Jiaotong University, Xi'an, China; Department of Medicine, The Second 
      Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
FAU - Zhan, Na
AU  - Zhan N
AD  - Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, China.
FAU - Ding, Dong
AU  - Ding D
AD  - Department of Gynecology, Hubei Maternity and Child Health Hospital, Wuhan, 
      China.
FAU - Liu, Xiaoming
AU  - Liu X
AD  - Department of Dermatology, The Third Affiliated Hospital of Soochow University, 
      Changzhou, China.
FAU - Zou, Xiaoyan
AU  - Zou X
AD  - Department of Dermatology, Hubei Maternity and Child Health Hospital, Wuhan, 
      China.
FAU - Li, Ke
AU  - Li K
AD  - Core Research Laboratory, The Second Affiliated Hospital, School of Medicine, 
      Xi'an Jiaotong University, Xi'an, China.
FAU - Xia, Yumin
AU  - Xia Y
AD  - Department of Dermatology, The Second Affiliated Hospital, School of Medicine, 
      Xi'an Jiaotong University, Xi'an, China. Electronic address: 
      xiayumin1202@163.com.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150527
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (TNFRSF12A protein, human)
RN  - 0 (TWEAK Receptor)
SB  - IM
MH  - Apoptosis/*genetics/physiology
MH  - Biopsy, Needle
MH  - Blotting, Western
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Flow Cytometry
MH  - Human papillomavirus 16/*isolation & purification
MH  - Humans
MH  - Immunohistochemistry
MH  - Keratinocytes/cytology/metabolism
MH  - Papillomavirus Infections/*pathology
MH  - Real-Time Polymerase Chain Reaction/methods
MH  - Receptors, Tumor Necrosis Factor/*genetics
MH  - Sensitivity and Specificity
MH  - TWEAK Receptor
MH  - Tissue Culture Techniques
MH  - Transfection
EDAT- 2015/05/29 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/05/29 06:00
PHST- 2015/02/02 00:00 [received]
PHST- 2015/05/15 00:00 [revised]
PHST- 2015/05/18 00:00 [accepted]
PHST- 2015/05/29 06:00 [entrez]
PHST- 2015/05/29 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - S0022-202X(15)41807-X [pii]
AID - 10.1038/jid.2015.201 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2015 Oct;135(10):2427-2436. doi: 10.1038/jid.2015.201. Epub 
      2015 May 27.