Abstract
Simple SummaryAbnormality of tight junction proteins closely contributes to epithelial–mesenchymal transition (EMT) and the malignancy of various cancers. Angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) is a novel molecular constituent of tricellular contacts that has a barrier function. Loss of angulin-1/LSR correlates with the malignancy in various cancers, including endometrioid-endometrial carcinoma (EEC). Moreover, loss of angulin-1/LSR upregulates claudin-1, and loss of apoptosis-stimulating p53 protein 2 (ASPP2) at tricellular contacts downregulates angulin-1/LSR in human EEC cell line Sawano. Angulin-1/LSR and ASPP2 concentrate at both midbody and centrosome during cytokinesis in Sawano. In EEC tissues, angulin-1/LSR and ASPP2 are reduced and claudin-2 is overexpressed during malignancy, while in the tissues of endometriosis changes in localization of angulin-1/LSR and claudin-2 are seen. This review highlights how the loss of angulin-1/LSR promotes the progression of endometriosis and EEC and discusses the possibility of therapeutic targeting for angulin-1/LSR via multiple signaling pathways and its related proteins.Tight junction proteins play roles beyond permeability barriers functions and control cell proliferation and differentiation. The relation between tight junctions and the signal transduction pathways affects cell growth, invasion and migration. Abnormality of tight junction proteins closely contributes to epithelial mesenchymal transition (EMT) and malignancy of various cancers. Angulin-1/lipolysis-stimulated lipoprotein receptor (LSR) forms tricellular contacts that has a barrier function. Downregulation of angulin-1/LSR correlates with the malignancy in various cancers, including endometrioid-endometrial carcinoma (EEC). These alterations have been shown to link to not only multiple signaling pathways such as Hippo/YAP, HDAC, AMPK, but also cell metabolism in ECC cell line Sawano. Moreover, loss of angulin-1/LSR upregulates claudin-1, and loss of apoptosis stimulating p53 protein 2 (ASPP2) downregulates angulin-1/LSR. Angulin-1/LSR and ASPP2 concentrate at both midbody and centrosome in cytokinesis. In EEC tissues, angulin-1/LSR and ASPP2 are reduced and claudin-2 is overexpressed during malignancy, while in the tissues of endometriosis changes in localization of angulin-1/LSR and claudin-2 are seen. This review highlights how downregulation of angulin-1/LSR promotes development of endometriosis and EEC and discusses about the roles of angulin-1/LSR and its related proteins, including claudins and ASPP2.
Highlights
Endometrial cancer (EC) is the most frequent neoplasia of the female genital tract in the world in 2018 [1], and its incidence in industrialized countries, as well as Japan, is recently increasing [1,2]
Loss of YAP prevents, the upregulation of AREG and TEAD1, and the cell migration and invasion induced by downregulation of LSR [11]. These findings show that the Hippo/YAP pathway is associated with cell migration and invasion in endometrial carcinoma (EEC) cells via upregulation of TEAD1/AREG induced by loss of angulin-1/LSR
Loss of angulin-1/LSR promotes the progression of endometriosis and EEC via multiple signaling pathways, Hippo/YAP, JNK, AMPK and histone deacetylases (HDAC), and CLDNs
Summary
Endometrial cancer (EC) is the most frequent neoplasia of the female genital tract in the world in 2018 [1], and its incidence in industrialized countries, as well as Japan, is recently increasing [1,2]. Further research on the pathophysiology of endometrial cancer must be conducted to develop novel therapies. Research in the field of molecular biology has recently been developing, and moleculartargeted therapy has become a new treatment strategy for various cancers. More studies are needed to determine the appropriate molecular-targeted therapy for EC, including identification of novel signal pathways in the progression of EC cells. Several studies have reported that expression of tight junction proteins plays an important role in the EMT of cancer cells [8]. These alterations are regulated via multiple signaling pathways such as.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
