HPV16 E7 oncogene expression in normal human epithelial cells causes molecular changes indicative of an epithelial to mesenchymal transition.
Cancer-associated epithelial to mesenchymal transition (EMT) is crucial for invasion and metastasis. Molecular hallmarks of EMT include down-regulation of the epithelial adhesion protein E-cadherin and de-novo expression of N-cadherin and the mesenchymal intermediate filament proteins vimentin and fibronectin. Expression of HPV16 E7 in normal human epithelial cells caused increased levels of vimentin and fibronectin, whereas the epithelial adhesion protein E-cadherin was expressed at decreased levels. Similar expression patterns of vimentin, fibronectin and E-cadherin were also detected in cells expressing HPV16 E6 and E7 or the entire HPV16 early transcriptional unit. HPV16 E6 and E7 were each able to induce N-cadherin expression. Interestingly, these changes in expression levels of EMT-associated proteins are not similarly reflected at the level of mRNA expression, suggesting that HPV16 oncoproteins also modulate EMT through non-transcriptional mechanisms. Hence, HPV16 oncoproteins may contribute to malignant progression through EMT induction.
Hellner
Karin
K
Infectious Diseases Division, The Channing Laboratories, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Mar
Jessica
J
Fang
Frank
F
Quackenbush
John
J
Münger
Karl
K
D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002472:Cell Transformation, Viral; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression; D005814:Genes, Viral; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D015820:Cadherins; C068651:E6 protein, Human papillomavirus type 16; D005353:Fibronectins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014746:Vimentin; C059731:oncogene protein E7, Human papillomavirus type 16