Chiu Hsiao-Chen, Li Chia-Jung, Yiang Giou-Teng, Tsai Andy Po-Yi, Wu Meng-Yu
Department of Obstetrics and Gynecology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei 231, Taiwan.
Department of Obstetrics and Gynecology, School of Medicine, Tzu Chi University, Hualien 970, Taiwan.
J Clin Med. 2019 Mar 30;8(4):439. doi: 10.3390/jcm8040439.
Endometrial carcinogenesis is involved in several signaling pathways and it comprises multiple steps. The four major signaling pathways-PI3K/AKT, Ras/Raf/MEK/ERK, WNT/β-catenin, and vascular endothelial growth factor (VEGF)-are involved in tumor cell metabolism, growth, proliferation, survival, and angiogenesis. The genetic mutation and germline mitochondrial DNA mutations also impair cell proliferation, anti-apoptosis signaling, and epithelial⁻mesenchymal transition by several transcription factors, leading to endometrial carcinogenesis and distant metastasis. The PI3K/AKT pathway activates the ransforming growth factor beta (TGF-β)-mediated endothelial-to-mesenchymal transition (EMT) and it interacts with downstream signals to upregulate EMT-associated factors. Estrogen and progesterone signaling in EMT also play key roles in the prognosis of endometrial carcinogenesis. In this review article, we summarize the current clinical and basic research efforts regarding the detailed molecular regulation in endometrial carcinogenesis, especially in EMT, to provide novel targets for further anti-carcinogenesis treatment.
子宫内膜癌发生涉及多个信号通路，且包含多个步骤。四大主要信号通路——磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）、Ras/Raf/丝裂原活化蛋白激酶激酶/细胞外信号调节激酶（Ras/Raf/MEK/ERK）、Wnt/β-连环蛋白以及血管内皮生长因子（VEGF）——参与肿瘤细胞代谢、生长、增殖、存活及血管生成。基因突变和种系线粒体DNA突变也通过多种转录因子损害细胞增殖、抗凋亡信号及上皮-间质转化，导致子宫内膜癌发生及远处转移。PI3K/AKT通路激活转化生长因子β（TGF-β）介导的内皮-间质转化（EMT），并与下游信号相互作用以上调EMT相关因子。EMT中的雌激素和孕激素信号在子宫内膜癌发生的预后中也起关键作用。在这篇综述文章中，我们总结了目前关于子宫内膜癌发生中详细分子调控，尤其是EMT的临床和基础研究成果，以提供进一步抗癌治疗的新靶点。
