Angiotensin II type 2 receptor–interacting protein 3a inhibits ovarian carcinoma metastasis via the extracellular HMGA2-mediated ERK/EMT pathway

Abstract

Local migration and long-distance metastasis is the main reason for higher mortality of ovarian cancer. Microtubule-associated tumor suppressor 1/angiotensin II type 2 receptor-interacting protein is associated with tumor initiation and progression and exerts anti-tumor effects. High mobility group AT-hook 2 is overexpressed in majority of metastatic carcinomas, which contributes to carcinomas metastasis through Snail-induced epithelial-to-mesenchymal transition signal pathway. The purpose of this study was to investigate the signal pathway of microtubule-associated tumor suppressor 1/angiotensin II type 2 receptor-interacting protein-mediated anti-tumor effects. Our data observed that ovarian carcinoma cells exhibited lower expression of angiotensin II type 2 receptor-interacting protein 3a and higher expression of high mobility group AT-hook 2 compared to normal ovarian cells. Restoration of angiotensin II type 2 receptor-interacting protein 3a expression in ovarian carcinoma cells inhibited high mobility group AT-hook 2 expression and exhibited anti-proliferative effects. In addition, angiotensin II type 2 receptor-interacting protein 3a treatment suppressed the phosphorylation of epithelial-to-mesenchymal transition and extracellular signal-regulated kinase in ovarian carcinoma cells. We also observed that angiotensin II type 2 receptor-interacting protein 3a restoration downregulated expression of Snail, E-Cadherin, N-Cadherin, and Vimentin in ovarian carcinoma cells, whereas angiotensin II type 2 receptor-interacting protein 3a knockdown enhanced the phosphorylation of extracellular signal-regulated kinase and epithelial-to-mesenchymal transition. In vivo assay indicated that angiotensin II type 2 receptor-interacting protein 3a inhibited ovarian tumor growth and elevated survival of tumor-bearing immunodeficient mice. Tumor histological analysis indicated that Snail, E-Cadherin, N-Cadherin, and Vimentin expression levels were downregulated via decreasing high mobility group AT-hook 2 expression. Furthermore, upregulation of angiotensin II type 2 receptor-interacting protein 3a impaired the phenotype of extracellular signal-regulated kinase and epithelial-to-mesenchymal transition in ovarian carcinoma cells and tumor tissues. Taken together, angiotensin II type 2 receptor-interacting protein 3a presents potential in suppressing the proliferation and aggressiveness of ovarian carcinoma cells through the high mobility group AT-hook 2-mediated extracellular signal-regulated kinase/epithelial-to-mesenchymal transition signal pathway.

The Tumor Suppressor MTUS1/ATIP1 Modulates Tumor Promotion in Glioma: Association with Epigenetics and DNA Repair

“…The function of ATIP1 as a TSG in glioma is substantiated by our observation that in glioma cells, elevated ATIP1 expression mitigates proliferation and clonogenic outgrowth as well as migration and invasion ( Figure 3 a–f) as has been demonstrated for several other tumors [ 31 , 32 , 33 ]. ATIP1 dramatically reduced glioma cell motility and enhanced cell adhesion at least partially by the construction of LFACs ( Figure 3 e,f).…”

Mitochondrial tumor suppressor 1 is a target of AT-rich interactive domain 1A and progesterone receptor in the murine uterus

“…ATIP3a is involved extracellular signal-regulated kinase (ERK) and epithelial-to-mesenchymal transition (EMT). Reconstitution of ATIP3 inhibits tumor growth, which led to an increase in survival rate in ovarian carcinoma via down-regulation of the ERK/EMT pathway [ 27 ]. When MTUS1/ATIP3 expression was restored, ATIP3 changed the velocity of cell division by prolonged metaphase, thereby leading to a reduced number of proliferative cells [ 28 ].…”

Angiotensin II and Angiotensin Receptors 1 and 2—Multifunctional System in Cells Biology, What Do We Know?

“…Ping et al noticed similar effect of AT2R in ovarian carcinoma. AT2R-interacting protein 3a blocked ovarian carcinoma migration and invasion by regulation of the ERK/EMT pathway [112]. In colorectal cancer, Ang II enhanced cell migration, however this effect was suppressed by AT1R and AT2R inhibitors [210].…”

“…Oh et al observed that in the xenograft model of breast cancer overexpression of AT1R was correlated with acceleration of tumor growth and increased expression of proliferation marker protein Ki67 (MKI67) [2]. In ovarian cancer, AT2R-interacting protein 3a inhibited proliferation of cells [112].…”