Pathological and Biomolecule Analyses Laboratory, Faculty of Pharmacy, Kindai University, Osaka, Japan.
Department of Molecular-Targeting Prevention, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Drug Discovery Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Biochem Biophys Res Commun. 2020 May 21;526(1):55-61. doi: 10.1016/j.bbrc.2020.03.065. Epub 2020 Mar 16.
Enhanced expression of cyclophilin A (CypA) in colorectal cancer (CRC) was reported; however, how CypA influences CRC progression is not clear. Therefore, we examine the effects of CypA on CRC cell progression. Knockdown of CypA in SW480 cells significantly inhibited cell migration and invasion but had no effect on cell proliferation. In addition, upregulation of E-cadherin and downregulation of N-cadherin and Snail expression were observed by CypA knockdown. These results suggested that CypA knockdown inhibited cell migration and invasion by suppressing epithelial-mesenchymal transition. CypA knockdown was also associated with increased p38 phosphorylation, and the p38 inhibitor treatment led to increase in the number of invasive CypA-knockdown SW480 cells. Therefore, CypA may be a potential therapeutic target in preventing CRC metastasis.
环孢素 A(CypA)在结直肠癌(CRC)中的表达增强已有报道;然而,CypA 如何影响 CRC 的进展尚不清楚。因此,我们研究了 CypA 对 CRC 细胞进展的影响。CypA 在 SW480 细胞中的敲低显著抑制了细胞迁移和侵袭,但对细胞增殖没有影响。此外,CypA 敲低导致 E-钙黏蛋白上调,N-钙黏蛋白和 Snail 表达下调。这些结果表明,CypA 敲低通过抑制上皮-间充质转化抑制细胞迁移和侵袭。CypA 敲低也与 p38 磷酸化增加有关,p38 抑制剂处理导致 CypA 敲低的 SW480 细胞侵袭数量增加。因此,CypA 可能是预防 CRC 转移的潜在治疗靶点。