Apoptosis-stimulating p53 protein 2 (ASPP2) is an apoptosis inducer that acts via binding with p53 and epithelial polarity molecule PAR3. Lipolysis-stimulated lipoprotein receptor (LSR) is an important molecule at tricellular contacts, and loss of LSR promotes cell migration and invasion via Yes-associated protein (YAP) in human endometrial cancer cells. In the present study, to find how ASPP2 suppression promotes malignancy in human endometrial cancer, we investigated its mechanisms including the relationship with LSR. In endometriosis and endometrial cancers (G1 and G2), ASPP2 was observed as well as PAR3 and LSR in the subapical region. ASPP2 decreased in G3 endometrial cancer compared to G1. In human endometrial cancer cell line Sawano, ASPP2 was colocalized with LSR and tricellulin at tricellular contacts and binding to PAR3, LSR, and tricellulin in the confluent state. ASPP2 suppression promoted cell migration and invasion, decreased LSR expression, and induced expression of phosphorylated YAP, claudin-1, -4, and -7 as effectively as the loss of LSR. Knockdown of YAP prevented the upregulation of pYAP, cell migration and invasion induced by the ASPP2 suppression. Treatment with a specific antibody against ASPP2 downregulated ASPP2 and LSR, affected F-actin at tricellular contacts, upregulated expression of pYAP and claudin-1, and induced cell migration and invasion via YAP. In normal human endometrial epithelial cells, ASPP2 was in part colocalized with LSR at tricellular contacts and knockdown of ASPP2 or LSR induced expression of claudin-1 and claudin-4. ASPP2 suppression promoted cell invasion and migration via LSR and YAP in human endometrial cancer cells.

中文翻译：

---

在人子宫内膜癌中，ASPP2抑制通过LSR和YAP促进恶性肿瘤。

促凋亡的p53蛋白2（ASPP2）是一种凋亡诱导剂，通过与p53和上皮极性分子PAR3结合而起作用。脂解刺激的脂蛋白受体（LSR）是三细胞接触处的重要分子，LSR的丢失通过人类子宫内膜癌细胞中的Yes相关蛋白（YAP）促进细胞迁移和侵袭。在本研究中，为了发现ASPP2抑制如何促进人类子宫内膜癌的恶性，我们研究了其机制，包括与LSR的关系。在子宫内膜异位和子宫内膜癌（G1和G2）中，在根尖下区域观察到ASPP2以及PAR3和LSR。与G1相比，G3子宫内膜癌中ASPP2降低。在人类子宫内膜癌细胞系Sawano中，ASPP2与LSR和三细胞蛋白在三细胞接触处共定位，并与PAR3，LSR，和三纤维素处于融合状态。抑制ASPP2促进细胞迁移和侵袭，降低LSR表达，并诱导磷酸化的YAP，claudin-1，-4和-7的表达与丢失LSR一样有效。抑制YAP可以防止pASP的上调，ASPP2抑制诱导的细胞迁移和侵袭。用针对ASPP2的特异性抗体处理会下调ASPP2和LSR，影响三细胞接触处的F-肌动蛋白，上调pYAP和claudin-1的表达，并通过YAP诱导细胞迁移和侵袭。在正常人子宫内膜上皮细胞中，ASPP2与LSR在三细胞接触处部分共定位，并且敲低ASPP2或LSR诱导claudin-1和claudin-4的表达。在人子宫内膜癌细胞中，ASPP2抑制通过LSR和YAP促进细胞侵袭和迁移。