Sobočan Monika, Smolle Maria Anna, Schatz Christoph, Haybaeck Johannes
Department of Pharmacology, Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia.
Division of Gynecology and Perinatology, University Medical Centre Maribor, 2000 Maribor, Slovenia.
Cancers (Basel). 2020 Jul 27;12(8):2074. doi: 10.3390/cancers12082074.
Endometrial cancer (EC) is a common gynecologic malignancy which continues to have a poor prognosis in advanced stages due to current therapeutic limitations. A significant mechanism of chemoresistance in EC has been shown to also be the enhancement of epithelial to mesenchymal transition (EMT) and the subsequent obtainment of stem cell-like characteristics of EC. Current evidence on EMT in EC however fails to explain the relationship leading to an EMT signaling enhancement. Our review therefore focuses on understanding eukaryotic translation initiation factors (eIFs) as key regulators of the translational process in enhancing EMT and subsequently impacting higher chemoresistance of EC. We identified pathways connected to the development of a microenvironment for EMT, inducers of the process specifically related to estrogen receptors as well as their interplay with eIFs. In the future, investigation elucidating the translational biology of EC in EMT may therefore focus on the signaling between protein kinase RNA-like ER kinase (PERK) and eIF2alpha as well as eIF3B.
子宫内膜癌（EC）是一种常见的妇科恶性肿瘤，由于目前治疗上的局限性，晚期患者的预后仍然很差。子宫内膜癌化疗耐药的一个重要机制是上皮-间质转化（EMT）增强以及随后获得类似干细胞的特征。然而，目前关于子宫内膜癌中EMT的证据未能解释导致EMT信号增强的关系。因此，我们的综述重点在于理解真核生物翻译起始因子（eIFs）作为翻译过程的关键调节因子在增强EMT以及随后影响子宫内膜癌更高化疗耐药性方面的作用。我们确定了与EMT微环境发展相关的途径、与雌激素受体特别相关的该过程诱导因子以及它们与eIFs的相互作用。因此，未来阐明子宫内膜癌在EMT中的翻译生物学的研究可能集中在蛋白激酶RNA样内质网激酶（PERK）与eIF2α以及eIF3B之间的信号传导上。
