Extracellular vesicular Wnt7b mediates HPV E6-induced cervical cancer angiogenesis by activating the ß-catenin signaling pathway.
J Exp Clin Cancer Res
; 39(1): 260, 2020 Nov 25.
Article
em En
| MEDLINE
| ID: mdl-33234148
ABSTRACT
BACKGROUND:
The E6 oncoproteins of human papillomavirus (HPV) 16/18 are the critical drivers of cervical cancer (CC) progression. Extracellular vesicles (EVs) are emerging as critical mediators of cancer-tumor microenvironment (TME) communication. However, whether EVs contribute to HPV 16/18 E6-mediated impacts on CC progression remains unclear.METHODS:
A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of EV-Wnt7b in HPV E6-induced CC angiogenesis. The prognostic value of serum EV-Wnt7b was determined and a predictive nomogram model was established.RESULTS:
HPV 16/18 E6 upregulated Wnt7b mRNA expression in four HPV 16/18-positive CC cell lines and their EVs. In vitro and in vivo experiments demonstrated that EV-Wnt7b mRNA was transferred to and modulated human umbilical vein endothelial cells (HUVECs) toward more proliferative and proangiogenic behaviors by impacting ß-catenin signaling. Clinically, serum EV-Wnt7b levels were elevated in CC patients and significantly correlated with an aggressive phenotype. Serum EV-Wnt7b was determined to be an independent prognostic factor for CC overall survival (OS) and recurrence-free survival (RFS). Notably, we successfully established a novel predictive nomogram model using serum EV-Wnt7b, which showed good prediction of 1- and 3-year OS and RFS.CONCLUSIONS:
Our results illustrate a potential crosstalk between HPV 16/18-positive CC cells and HUVECs via EVs in the TME and highlight the potential of circulating EV-Wnt7b as a novel predictive biomarker for CC prognosis.Palavras-chave
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MEDLINE
Assunto principal:
Proteínas Repressoras
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Neoplasias do Colo do Útero
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Proteínas Oncogênicas Virais
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Proteínas de Ligação a DNA
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Proteínas Wnt
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Beta Catenina
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Vesículas Extracelulares
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article