Notch and Endometrial Cancer
The human endometrium is a unique, highly dynamic tissue that undergoes cyclic changes of cell proliferation, differentiation, and death. Endometrial cancer is the most common malignancy among women in developed countries. Importantly, the incidence of en
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Notch and Endometrial Cancer Violeta Jonusiene and Ausra Sasnauskiene
Abstract
The human endometrium is a unique, highly dynamic tissue that undergoes cyclic changes of cell proliferation, differentiation, and death. Endometrial cancer is the most common malignancy among women in developed countries. Importantly, the incidence of endometrial cancer is rising in high-income countries. Currently histological classification is used for subtyping of endometrial cancer, while ongoing research is evaluating markers for more accurate molecular classification. Evolutionary conserved Notch signaling pathway regulates diverse cellular processes such as proliferation, differentiation, and cell invasion. Accumulating evidence links aberrant Notch signaling with diseases such as hyperplasia and endometrial cancer. This chapter summarizes the current state of Notch signaling investigations in the endometrium, endometriosis, and endometrial cancer. Keywords
Notch · Endometrium · Endometrial cancer · Endometriosis · Stem cells · Leptin
V. Jonusiene (*) · A. Sasnauskiene Vilnius University, Life Sciences Center, Institute of Biosciences, Vilnius, Lithuania e-mail: [email protected]
otch Signaling in the Normal N Endometrium The human endometrium is a unique, dynamic system that undergoes cyclic changes regulating cell proliferation, differentiation, and death during every menstrual cycle and pregnancy. Physiological changes that occur in fertile women are tightly regulated by hormones, specifically estrogen, progesterone, and chorionic gonadotropin (Banerjee and Fazleabas 2011; Maruyama and Yoshimura 2008). Therefore, it is not surprising that evolutionary conserved Notch pathway, due to its role in proliferation, differentiation, and angiogenesis, is actively involved in endometrium remodeling as well as in diseases such as hyperplasia and cancer. Morphologically the endometrium is divided into functional and basal layers. The functional layer occupies two-thirds of the endometrial thickness and it is responsible for proliferation and secretion. During menstruations, the functional layer separates from the basal layer, while the basal layer serves as a base for endometrial regeneration and remains intact during menstruation. The endometrium is composed of different compartments: the luminal and the glandular epithelium, the stroma with stromal fibroblastic cells, and the vascular compartment (Diedrich et al. 2007; Ruiz-Alonso et al. 2012). Notch is crucial for uterine development. In fact, it was shown that overexpression of
© Springer Nature Switzerland AG 2021 J. Reichrath, S. Reichrath (eds.), Notch Signaling in Embryology and Cancer, Advances in Experimental Medicine and Biology 1287, https://doi.org/10.1007/978-3-030-55031-8_4
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V. Jonusiene and A. Sasnauskiene
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NICD1 in mouse uterus leads to complete infertility, absence of uterine glands, and dysregulation of progesterone and estrogen signaling (Su et al. 2016). Mikhailik et al. have examined transcripts and demonstrated that Notch signaling is acti
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