Zglejc-Waszak Kamila, Jozwik Marcin, Thoene Michael, Wojtkiewicz Joanna
Department of Anatomy, Faculty of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland.
Department of Gynecology and Obstetrics, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-045 Olsztyn, Poland.
Cancers (Basel). 2024 Sep 19;16(18):3192. doi: 10.3390/cancers16183192.
Endometrial cancer (EC) is the most common gynecological malignancy. EC is associated with metabolic disorders that may promote non-enzymatic glycation and activate the receptor for advanced glycation end-products (RAGE) signaling pathways. Thus, we assumed that RAGE and its ligands may contribute to EC. Of particular interest is the interaction between diaphanous-related formin 1 (Diaph1) and RAGE during the progression of human cancers. Diaph1 is engaged in the proper organization of actin cytoskeletal dynamics, which is crucial in cancer invasion, metastasis, angiogenesis, and axonogenesis. However, the detailed molecular role of RAGE in EC remains uncertain. In this review, we discuss epigenetic factors that may play a key role in the RAGE-dependent endometrial pathology. We propose that DNA methylation may regulate the activity of the RAGE pathway in the uterus. The accumulation of negative external factors, such as hyperglycemia, inflammation, and oxidative stress, may interfere with the DNA methylation process. Therefore, further research should take into account the role of epigenetic mechanisms in EC progression.
子宫内膜癌（EC）是最常见的妇科恶性肿瘤。EC与代谢紊乱有关，代谢紊乱可能会促进非酶糖基化并激活晚期糖基化终产物受体（RAGE）信号通路。因此，我们推测RAGE及其配体可能与EC有关。在人类癌症进展过程中，尤其是丝状肌动蛋白相关成束蛋白1（Diaph1）与RAGE之间的相互作用备受关注。Diaph1参与肌动蛋白细胞骨架动力学的正常组织，这在癌症侵袭、转移、血管生成和轴突形成中至关重要。然而，RAGE在EC中的详细分子作用仍不确定。在本综述中，我们讨论了可能在RAGE依赖性子宫内膜病理中起关键作用的表观遗传因素。我们提出DNA甲基化可能调节子宫中RAGE途径的活性。高血糖、炎症和氧化应激等负面外部因素的积累可能会干扰DNA甲基化过程。因此，进一步的研究应考虑表观遗传机制在EC进展中的作用。
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