Overexpression of carbonyl reductase 1 inhibits malignant behaviors and epithelial mesenchymal transition by suppressing TGF‑β signaling in uterine leiomyosarcoma cells

Abstract

Carbonyl reductase 1 (CBR1) has been reported to be involved in cancer progression. Recently, we found that CBR1 overexpression inhibited malignant behaviors and the epithelial mesenchymal transition (EMT) in uterine cervical cancer. It remained unclear whether this was also the case in uterine leiomyosarcoma (uLMS), which is derived from mesenchymal cells and is a much more malignant gynecological tumor. A number of previous studies suggested that malignant behaviors are associated with EMT, even in mesenchymal malignant tumors. In the present study, we investigated whether CBR1 inhibits malignant behaviors and EMT in uLMS. We established clones of uLMS cells (SKN cells) and uterine sarcoma cells (MES-SA cells) that overexpressed CBR1. Cell proliferative, migratory and invasive activities were suppressed by CBR1 overexpression, accompanied by increases in the expressions of epithelial markers (E-cadherin and cytokeratin) and decreases in the expressions of mesenchymal markers (N-cadherin and fibronectin), suggesting that CBR1 overexpression inhibits malignant behaviors and EMT in uLMS cells. In addition, transforming growth factor-β (TGF-β) production and the subsequent signaling and phosphorylation of Smad were suppressed in the clones. To investigate the association between TGF-β and EMT, SKN cells were treated with TGF-β or a TGF-β receptor blocker (SB431542). EMT was promoted by TGF-β and inhibited by SB431542. In conclusion, this is the first study, to the best of the authors' knowledge, showing that CBR1 overexpression inhibits malignant behaviors and EMT in uLMS cells. The present study provided novel insight demonstrating that the suppressive effect of CBR1 is mediated through TGF-β signaling.

Psychological Nursing Effect of Patients with Gynecological Malignant Tumor

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Effects of Maternal Nicotine Exposure on Fibronectin Expression in the Kidney of Mouse Newborns in Embryonic and Milking Period

“…Deng et al reported that nicotine could inhibit matrix synthesis in the cartilaginous plate and reduce insulinlike growth factor expression resulting in delayed chondrogenesis, a decline in growth, and consequent weight loss at birth (7). The relationship between cytokines, such as transforming growth factor-beta (TGF-β1), and fibronectin expression have been previously reported, and the observed changes in fibronectin expression could be attributed to the effect of nicotine on these cytokines (15). TGF-β1, through downstream signals that belong to the protein family of Smads, initiates their activity by Smads2/3 phosphorylation (16).…”

Effects of Induced Exosomes from Endometrial Cancer Cells on Tumor Activity in the Presence of Aurea helianthus Extract

“…Unlike tocopherol-α and rutin, AH, particularly AH1000, significantly downregulated SCC and UGF ( Figure 1 ). SCC binds to carbonyl reductase, which inhibits malignant behavior and TGF-β signaling in uterine cancer cells [ 25 ].…”