Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 1 via Montellier, 00133 Rome, Italy.
Int J Mol Sci. 2021 Dec 17;22(24):13543. doi: 10.3390/ijms222413543.
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.
伤口愈合需要静态上皮细胞通过一个多步骤过程逐渐获得移动表型，这个过程称为上皮-间质转化 (EMT)。尽管 EMT 本质上是短暂和可逆的，但当上皮细胞长期暴露于病原体时，它会持续存在并异常激活：这种事件会深刻改变组织，最终导致疾病的发展。其中许多疾病包括子宫颈鳞状细胞癌 (SCC)，这是女性生殖系统最常见的恶性肿瘤。SCC 的发病与高危型人乳头瘤病毒 (HR-HPV) 持续感染子宫颈有关，常常复发和/或转移，对常规化疗或放疗有抗性。鉴于这些可怕的临床特征至少部分可能源于 HPV 感染子宫颈中发生的加剧和持久的 EMT；在这里，我们已经审查了关于 HPV 致癌蛋白、细胞肿瘤抑制因子、基因表达调节剂、炎症细胞因子或生长因子，以及这些效应物之间相互作用对 EMT 诱导和子宫颈癌发生的影响的已发表研究。可以预见且期望的是，更广泛地了解 EMT 诱导物在 SCC 发病机制中的作用将为针对这种侵袭性肿瘤的新策略提供指导。
