Infection by High-Risk Human Papillomaviruses, Epithelial-to-Mesenchymal Transition and Squamous Pre-Malignant or Malignant Lesions of the Uterine Cervix: A Series of Chained Events?

Abstract

Wound healing requires static epithelial cells to gradually assume a mobile phenotype through a multi-step process termed epithelial-to-mesenchymal transition (EMT). Although it is inherently transient and reversible, EMT perdures and is abnormally activated when the epithelium is chronically exposed to pathogens: this event deeply alters the tissue and eventually contributes to the development of diseases. Among the many of them is uterine cervical squamous cell carcinoma (SCC), the most frequent malignancy of the female genital system. SCC, whose onset is associated with the persistent infection of the uterine cervix by high-risk human papillomaviruses (HR-HPVs), often relapses and/or metastasizes, being resistant to conventional chemo- or radiotherapy. Given that these fearsome clinical features may stem, at least in part, from the exacerbated and long-lasting EMT occurring in the HPV-infected cervix; here we have reviewed published studies concerning the impact that HPV oncoproteins, cellular tumor suppressors, regulators of gene expression, inflammatory cytokines or growth factors, and the interactions among these effectors have on EMT induction and cervical carcinogenesis. It is predictable and desirable that a broader comprehension of the role that EMT inducers play in SCC pathogenesis will provide indications to flourish new strategies directed against this aggressive tumor.

HIV-1 Proteins gp120 and Tat Promote Epithelial-Mesenchymal Transition and Invasiveness of HPV-Positive and HPV-Negative Neoplastic Genital and Oral Epithelial Cells

“…Cancer-associated EMT is a multistep process, which begins with the loss of apicobasal polarity in epithelial cells, followed by the loss of adherens and tight junctions, epithelial markers, and cell adhesion. During the final stages of EMT, cells acquire a spindle cell morphology and express mesenchymal markers ( 14 – 19 ). Cells in intermediate stages of EMT may express both epithelial E-cadherin and mesenchymal vimentin markers and thus present a hybrid phenotype; this is a critical factor contributing to the invasiveness of cancer cells ( 14 – 19 ).…”

“…During the final stages of EMT, cells acquire a spindle cell morphology and express mesenchymal markers ( 14 – 19 ). Cells in intermediate stages of EMT may express both epithelial E-cadherin and mesenchymal vimentin markers and thus present a hybrid phenotype; this is a critical factor contributing to the invasiveness of cancer cells ( 14 – 19 ).…”

Development and validation of an autophagy-related long non-coding RNA prognostic signature for cervical squamous cell carcinoma and endocervical adenocarcinoma

“…be deemed a vital element in cervical cancer pathogenesis (23). Epithelial-mesenchymal transition was an important step in the process of cervical-epithelial carcinogenesis (24). The study of Xie et al also showed that the 2M checkpoint pathway was associated with CESC (25).…”

“…In the study of Xiong et al., the Rb-E2F pathway could be deemed a vital element in cervical cancer pathogenesis ( 23 ). Epithelial–mesenchymal transition was an important step in the process of cervical–epithelial carcinogenesis ( 24 ). The study of Xie et al.…”

Update on the Epidemiological Features and Clinical Implications of Human Papillomavirus Infection (HPV) and Human Immunodeficiency Virus (HIV) Coinfection

“…On the one hand, the E6 protein binds p53, a major negative regulator of cell growth. The loss of p53 activity leads to uncontrolled cellular cycling, allowing chromosomal mutations to accumulate without DNA repair [ 31 ]. On the other, E7 protein targets p130, another negative cell-cycle regulator, thereby increasing cell growth and promoting uncontrolled proliferation [ 32 ].…”