Human papillomavirus type 16 oncoprotein E7 suppresses cadherin-mediated cell adhesion via ERK and AP-1 signaling.
Human papillomaviruses (HPV) are the main etiological factor for cervical carcinoma. HPV-16 is the most prevalent high-risk HPV-genotype found in HPV-associated cancers. We studied the effect of HPV-16 E7 oncoprotein on cadherin-mediated cell adhesion. The expression of E7 strongly suppressed the cadherin-mediated cell adhesion in the rat fibroblast cell line 3Y1. This suppression was associated with the decreased expression of N-cadherin at the transcriptional level. The treatment of 3Y1 cells that express E7 (E7-3Y1) with MEK inhibitor recovered the cadherin-mediated cell adhesion together with the accumulation of N-cadherin at the cell-cell contact site. Moreover, the suppression of c-Jun, which is the element of AP-1 transcriptional factor, leads to the recovery of N-cadherin expression and cadherin-mediated cell adhesion in E7-3Y1 cells. Taken together, our results demonstrate that E7 regulates cadherin-mediated cell adhesion through the modulation of cadherin expression via the MEK-ERK and AP-1 signaling pathway.
Yuan
Hong
H
Division of Cancer Biology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
Ito
Satoko
S
Senga
Takeshi
T
Hyodo
Toshinori
T
Kiyono
Tohru
T
Kikkawa
Fumitaka
F
Hamaguchi
Michinari
M
D000818:Animals; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D050725:Papillomavirus E7 Proteins; D051381:Rats; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000502:physiology*
D015820:Cadherins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D018808:Transcription Factor AP-1; C059731:oncogene protein E7, Human papillomavirus type 16; D048049:Extracellular Signal-Regulated MAP Kinases