Lipolysis-stimulated lipoprotein receptor (LSR) is a unique molecule of tricellular contacts of normal and cancer cells. We investigated how the loss of LSR induced cell migration, invasion and proliferation in endometrial cancer cell line Sawano. mRNAs of amphiregulin (AREG) and TEA domain family member 1 (TEAD1) were markedly upregulated by siRNA-LSR. In endometrial cancer tissues, downregulation of LSR and upregulation of AREG were observed together with malignancy, and Yes-associated protein (YAP) was present in the nuclei. siRNA-AREG prevented the cell migration and invasion induced by siRNA-LSR, whereas treatment with AREG induced cell migration and invasion. LSR was colocalized with TRIC, angiomotin (AMOT), Merlin and phosphorylated YAP (pYAP). siRNA-LSR increased expression of pYAP and decreased that of AMOT and Merlin. siRNA-YAP prevented expression of the mRNAs of AREG and TEAD1, and the cell migration and invasion induced by siRNA-LSR. Treatment with dobutamine and 2-deoxy-D-glucose and glucose starvation induced the pYAP expression and prevented the cell migration and invasion induced by siRNA-LSR. siRNA-AMOT decreased the Merlin expression and prevented the cell migration and invasion induced by siRNA-LSR. The loss of LSR promoted cell invasion and migration via upregulation of TEAD1/AREG dependent on YAP/pYAP and AMOT/Merlin in human endometrial cancer cells.

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.

Male fetuses generally grow faster in utero and are heavier at birth than females, whereas the rates of perinatal mortality and morbidity are often higher in boys than in girls. Sexual dimorphism in placental function is believed to contribute to these differences. However, evidence for sex-specific differences in placental function remains limited. We hypothesized that placental nutrient-sensing signaling activity, amino acid transport capacity, and mitochondrial respiration are higher in male than female placentas. Placentas were collected from 46 women (BMI 18.5–29.9 kg/m²) with uncomplicated pregnancies delivering appropriate-for-gestational-age infants (n = 23 female; n = 23 male). In homogenates of male placentas, the phosphorylation of S6RP (Ser235/236) was increased and total 4E-BP1 protein expression was reduced compared with female placentas, indicating enhanced mTORC1 signaling. In vitro System A amino acid transport activity was also greater in microvillous plasma membranes isolated from male placentas. Placental mitochondrial respiratory capacity was assessed in villous tissue using high-resolution respirometry with carbohydrate and lipid substrate–uncoupler–inhibitor titration (Carb SUIT and Lipid SUIT) protocols on the Oroboros O2k platform. Male placentas exhibited greater maximal oxidative phosphorylation capacity, enhanced complex II-linked respiration, and higher maximal electron transport system capacity compared with female placentas under both carbohydrate- and lipid-supported respiratory conditions. Although placental weight did not differ between sexes, the birth weight-to-placental weight ratio was significantly higher in male pregnancies, consistent with greater placental functional efficiency. In conclusion, placental mTORC1 signaling activity, System A amino acid transport activity, and mitochondrial respiratory capacity are greater in male than female placentas and are associated with greater placental functional efficiency and fetal growth in male pregnancies.