Effects of HPV-16 E5, E6 and E7 proteins on survival, adhesion, migration and invasion of trophoblastic cells.
Among high-risk human papillomaviruses (HPV), HPV-16 infection is the most prevalent causative factor for cervical cancer. Beside other mucosal targets, HPV-16 was reported to infect the placenta and to replicate in trophoblastic cells. Since these cells share invasive properties of tumoral cells, they represent an ideal model to investigate several oncogenic processes. In the present work, we analyzed the impacts of HPV-16 E5, E6 and E7 oncoproteins on the trophoblastic model. Our results showed that E5 impaired the viability of trophoblastic and cervical cell lines but E6 and E7, favoring cell growth, neutralized the E5 cytotoxic effect. In addition, E5 decreased the adhesiveness of trophoblastic cells to the tissue culture plastic and to endometrial cells similarly as described previously for E6 and E7. E5 and E6 plus E7 increased also their migration and their invasive properties. Cells expressing HPV-16 early proteins under the control of the long control region endogenous promoter displayed growth advantage and were also more motile and invasive compared with control cells. Interestingly, the E-cadherin was downregulated in trophoblastic cells expressing E5, E6 and E7. Nuclear factor-kappaB and activator protein-1 activities were also enhanced. In conclusion, HPV-16 early proteins enhanced trophoblastic growth and intensify the malignant phenotype by impairing cell adhesion leading to increased cellular motile and invasive properties. HPV-16 E5 participated, with E6 and E7, in these changes by impairing E-cadherin expression, a hallmark of malignant progression.
Boulenouar
Selma
S
Research Laboratory on Human Reproduction, Université Libre de Bruxelles, Route de Lennik 808, CP636, B-1070 Brussels, Belgium.
Weyn
Christine
C
Van Noppen
Melody
M
Moussa Ali
Mohamed
M
Favre
Michel
M
Delvenne
Philippe O
PO
Bex
Françoise
F
Noël
Agnès
A
Englert
Yvon
Y
Fontaine
Véronique
V
D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion; D045744:Cell Line, Tumor / Q000166:cytology / Q000821:virology; D002633:Chemotaxis / Q000502:physiology; D002822:Choriocarcinoma / Q000473:pathology*; D003588:Cytopathogenic Effect, Viral; D016889:Endometrial Neoplasms / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D052162:Human papillomavirus 16 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D050725:Papillomavirus E7 Proteins / Q000502:physiology*; D010641:Phenotype; D012097:Repressor Proteins / Q000502:physiology*; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D014594:Uterine Neoplasms / Q000473:pathology*; D000086082:Viroporin Proteins
D015820:Cadherins; D009363:Neoplasm Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C068651:E6 protein, Human papillomavirus type 16; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins; C059731:oncogene protein E7, Human papillomavirus type 16