The role of human papillomavirus type 16 E6/E7 oncoproteins in cervical epithelial-mesenchymal transition and carcinogenesis

Abstract

Abstract. Cervical cancer is the most common malignancy in females worldwide. This study investigated the prevalence of the E6/E7 oncoproteins of human papillomavirus (HPV) type 16, which are important in fibroblast growth factor (FGF) 2-and 4-induced epithelial-mesenchymal transition (EMT) and cervical tumorigenesis. We investigated the functional interaction between HPV16 E6/E7-transfected Cx cells (CxWJ cells) and treatment with FGF2 and 4, according to the expression of α-smooth muscle actin (α-SMA), vimentin and E-cadherin protein as well as cell growth and invasive ability. The results showed the upregulation of α-SMA and vimentin and the downregulation of E-cadherin protein expression in CxWJ cells. HPV16 E6/E7 infection partially repressed proliferation, but not the invasive ability of FGF2 or FGF4 stimulation in cervical cancer cells (CxWJ cells). These data provide evidence of a functional interaction between HPV16 E6/E7 and FGFs 2 and 4, suggesting that cooperative stimulation of HPV E6/E7 and FGFs activated in human cervical cancer cells is required to completely overcome the oncogenic function associated with the development of cervical epithelial-mesenchymal transition and tumorigenesis.

EMT in cervical cancer: Its role in tumour progression and response to therapy

“…Cervical cancer cells transfected with HPV16 E6 and E7 experience morphological changes and changes in the expression levels of α-SMA, Vim1 (up-regulated) and E-cadherin (down-regulated) that correspond to EMT induction [26]. In addition, HPV16 E7 in combination with low dose oestrogen, FGF-2 and FGF-4 administration is sufficient for the induction of invasive cervical carcinomas [26].…”

“…HPV proteins and fibroblast growth factor (FGF) may directly contribute to EMT induction [25] by inducing phenotypic features and molecular programs in normal cultured keratinocytes. Thus, they cooperatively act to inhibit E-cadherin and induce Vim1 expression [26,27]. A number of findings indicate that the EMT of epithelial cancers correlates with aggressive tumours in patients with cervical cancer.…”

Long Pentraxin-3 Inhibits Epithelial–Mesenchymal Transition in Melanoma Cells

“…Also, we provide novel insights about the role of the FGF2/FGFR1 system in melanoma progression by showing that PTX3 overexpression inhibits EMT in these cells. The FGF/FGFR system has been shown to modulate EMT in breast (37), cervical (38), colon (39), bladder (40), and prostate (41) cancer. To the best of our knowledge, our data provide the first experimental evidence about a nonredundant role of the FGF/FGFR system in the modulation of the EMT process in melanoma.…”

The epithelial–mesenchymal transition (EMT) is regulated by oncoviruses in cancer

“…In addition, E6/E7 reportedly prompt fibroblast growth factor (FGF) 2-and -4-induced EMT and cervical tumorigenesis (37). HPV16 E6/E7 transfection repressed the expression of the E-cadherin protein in cervical cancer cells, caused FGF ligand stimulation, and increased invasive ability (37). In head and neck squamous cell carcinoma (HNSCC), HPV + represents a distinct clinical and epidemiologic condition compared with HPV 2 HNSCC.…”