Endometrial Carcinogenesis and Molecular Signaling Pathways

Abstract

The Endometrial Cancer (EC) is the most common gynecologic malignancy that starts in the endometrium of women. Carcinogenesis of EC is associated with several critical regulatory molecules, which involve in different signaling pathways. A number of signaling pathways have been identified to be involved in the multiple-step development of EC, including PI3K/AKT/mTOR signaling pathway, WNT/β-catenin signal transduction cascades (including APC/β-catenin pathway), MAPK/ ERK pathway, VEGF/VEGFR ligand receptor signaling pathway, ErbB signaling pathway, P53/P21 and P16INK4a/pRB signaling pathways. This review mainly focuses on the molecular signaling pathways relevant to human endometrial cancer and discusses those critical capabilities of transforming endometrial cells, including evading apoptosis; enhancing cell proliferation; blocking differentiation; and inducing angiogenesis.

Comparative characteristics of the transcriptional activity of CDH1, CTNNB1, VEGFA genes and expression of proteins E-cadherin, β-catenin and VEGFA, coded by these genes in metastatic and non-metastatic endometrioid endometrial carcinoma

“…Иммуногистохимическим методом изучены инвазивная рТ [1][2][3][4] N 0 M x G 1-3 эндометриоидная аденокар-цинома эндометрия (ЭАЭ) (n=56; возраст -42-83 года), инвазивная рТ 1-4 N 1-2 M x G 1-3 ЭАЭ (n=30; возраст -48-79 лет) и образцы эндометрия фазы пролиферации (ПЕ) (n=30; возраст -41-62 года). Молекулярно-генетическим методом изучены инвазивная рТ [1][2][3][4] N 0 M x ЭАЭ (n=10; возраст -45-67 лет), инвазивная рТ 1-4 N 1-2 M x ЭАЭ (n=10; возраст -44-63 года) и образцы ПЕ (n=10; возраст -46-59 лет).…”

“…T he features of endometrial carcinogenesis, in which the violation of Wnt-signaling pathway and the violation of cyclic neoangiogenesis are ones of the earliest events, have become the subject of many researches in recent years [1,2]. It is known that epigenetic modifi cations and also mutations of β-catenin and E-cadherin genes (CTNNB1 and CDH1 accordingly), that encode molecules which regulate cell polarity and provide reorganization of the cytoskeleton, and also encode intercellular adhesion molecules which ensure the maintenance of normal tissues histoarchitectonics, play an important role in the carcinogenesis of endometrioid endometrial carcinoma (EEC) [3][4][5][6]. CTNNB1 gene encodes β-catenin, which is an intercellular adhesion molecule and a transcription factor of the canonical Wnt-signaling pathway [7].…”

“…One of the most powerful pro-angiogenic factors, which are involved in the angiogenesis during type 1 endometrial cancer, is vascular endothelial growth factor (VEGF) [12]. The angiogenesis, which progresses in the endometrial cancer, is supposed by the alteration in VEGF/VEGF-receptors signaling pathways [3], the participation of WNT-proteins and β-catenin, but the role of inhibitors and inducers of Wnt-signaling pathway in this process is still unknown [22].…”

Analysis of Plant-derived Phytochemicals as Anti-cancer Agents Targeting Cyclin Dependent Kinase-2, Human Topoisomerase IIa and Vascular Endothelial Growth Factor Receptor-2

“…Since VEGF mediates its effects by binding to specific receptors (like VEGFR-2), inhibiting the actions of the receptors is thought to be a therapeutic target for cancer treatment (85). When VEGF protein binds with VEGFR-2, the VEGFR-2 becomes activated which then activates phosphatidylinositol Figure 03) (86,87,88). Since VEGFR-2 is involved in angiogenesis process in cancer development, inhibition of VEGFR-2 is considered as therapeutic approach to treat cancer.…”

Nanoparticle encapsulation of HDACi with HA targeting in endometrial cancer models

“…Nieminen et al [13], identi ed 24 tumour suppressor genes that were progressively hypermethylated during the development of type I endometrial cancer [15,18,19]. Similarly, treatment of endometrial cancer models using small chemical compounds that modify epigenetic processes can partially, or even fully, restore the normal expression levels of genes including the re-expression of inactivated tumour suppressor genes and deactivation of activated oncogenes [20,21].…”