Al-Kuraishy Hayder M, Al-Maiahy Thabat J, Al-Gareeb Ali I, Alexiou Athanasios, Papadakis Marios, Saad Hebatallah M, Batiha Gaber El-Saber
Department of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq.
Department of Gynecology and Obstetrics, College of Medicine, Mustansiriyah University, Baghdad, Iraq.
Cancer Rep (Hoboken). 2024 Jan;7(1):e1920. doi: 10.1002/cnr2.1920. Epub 2023 Nov 28.
Endometrial adenocarcinoma (EAC) is a malignant tumor of the endometrium. EAC is the most common female malignancy following the menopause period. About 40% of patients with EAC are linked with obesity and interrelated with hypertension, diabetes mellitus, and high circulating estrogen levels. Proprotein convertase (PC) furin was involved in the progression of EAC.
Furin is a protease enzyme belonging to the subtilisin PC family called PC subtilisin/kexin type 3 that converts precursor proteins to biologically active forms and products. Aberrant activation of furin promotes abnormal cell proliferation and the development of cancer. Furin promotes angiogenesis, malignant cell proliferation, and tissue invasion by malignant cells through its pro-metastatic and oncogenic activities. Furin activity is correlated with the malignant proliferation of EAC. Higher expression of furin may increase the development of EAC through overexpression of pro-renin receptors and disintegrin and metalloprotease 17 (ADAM17). As well, inflammatory signaling in EAC promotes the expression of furin with further propagation of malignant transformation.
Furin is associated with the development and progression of EAC through the induction of proliferation, invasion, and metastasis of malignant cells of EAC. Furin induces ontogenesis in EAC through activation expression of ADAM17, pro-renin receptor, CD109, and TGF-β. As well, EAC-mediated inflammation promotes the expression of furin with further propagation of neoplastic growth and invasion.
子宫内膜腺癌（EAC）是子宫内膜的一种恶性肿瘤。EAC是绝经后最常见的女性恶性肿瘤。约40%的EAC患者与肥胖有关，并与高血压、糖尿病和高循环雌激素水平相关。前蛋白转化酶（PC）弗林蛋白酶参与了EAC的进展。
弗林蛋白酶是一种属于枯草杆菌蛋白酶PC家族的蛋白酶，称为PC枯草杆菌蛋白酶/凯新3型，可将前体蛋白转化为生物活性形式和产物。弗林蛋白酶的异常激活促进异常细胞增殖和癌症发展。弗林蛋白酶通过其促转移和致癌活性促进血管生成、恶性细胞增殖以及恶性细胞的组织侵袭。弗林蛋白酶活性与EAC的恶性增殖相关。弗林蛋白酶的高表达可能通过前肾素受体以及解整合素和金属蛋白酶17（ADAM17）的过表达增加EAC的发展。同样，EAC中的炎症信号促进弗林蛋白酶的表达，进一步推动恶性转化。
弗林蛋白酶通过诱导EAC恶性细胞的增殖、侵袭和转移与EAC的发生和进展相关。弗林蛋白酶通过激活ADAM17、前肾素受体、CD109和转化生长因子-β的表达诱导EAC的发生。同样，EAC介导的炎症促进弗林蛋白酶的表达，进一步推动肿瘤生长和侵袭。
