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首页> 外文期刊>Biochemical Pharmacology >Esculetin suppresses tumor growth and metastasis by targeting Axin2/E-cadherin axis in colorectal cancer
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Esculetin suppresses tumor growth and metastasis by targeting Axin2/E-cadherin axis in colorectal cancer

机译：Esculetin通过靶向甲蛋白2 / E-Cadherin轴在结肠直肠癌中抑制肿瘤生长和转移

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Colorectal cancer (CRC) is the most common malignant disease worldwide due to its metastasis via the epithelial-mesenchymal transition (EMT) process. E-cadherin and Wnt signaling are emerging as potential targets for suppressing the EMT. In this context, Axin2 has been recognized as a negative regulator that inhibits glycogen synthase kinase 3 beta (GSK3 beta)-mediated degradation of Snaill, a transcriptional repressor of E-cadherin. However, Axin2 can also impede Wnt signaling via beta-catenin degradation. Therefore, Axin2 may serve as either a promoter or suppressor of tumors, and the effects of its inhibition on the cell proliferation and metastasis of CRC require further elucidation. Here, esculetin (ES), a coumarin, was found to have the most potential effects on both beta-catenin-responsive transcriptional and E-cadherin promoter activities. ES also showed anti-pro-liferative and anti-invasive activities in CRC cells. Mechanistically, Axin2 suppression by ES contributed to E-cadherin-mediated Wnt signaling inhibition. Moreover, the ability of ES to inhibit tumor growth and metastasis via Axin2 suppression was further supported in an HCT116-implanted orthotopic mouse model. Collectively, these findings suggest that targeting the Axin2/E-cadherin axis by ES may be an attractive therapeutic strategy for the treatment of metastatic CRC.
机译：结肠直肠癌（CRC）是全世界最常见的恶性疾病，由于其转移通过上皮 - 间充质转换（EMT）过程。 E-Cadherin和WNT信号传导是抑制EMT的潜在目标。在这种情况下，AXIN2已被识别为抑制糖原合酶激酶3β（GSK3β）介导的Snaill的降解，E-Cadherin的转录压缩机。然而，Axin2还可以通过β-catenin降解妨碍Wnt信号传导。因此，AXIN2可以用作肿瘤的启动子或抑制剂，并且其抑制对CRC的细胞增殖和转移的影响需要进一步阐明。这里，发现eSculetin（ES），一种香豆素，对β-连环蛋白响应性转录和E-Cadherin启动子活性具有最大的潜在影响。 ES还显示CRC细胞中的抗救生和抗侵袭性活性。机械地，通过ES抑制抑制促进了E-Cadherin介导的WNT信号传导抑制。此外，在HCT116植入的原位小鼠模型中进一步支持ES抑制肿瘤生长和转移的能力。总的来说，这些发现表明，靶向轴2 / E-钙粘蛋白轴通过ES可以是治疗转移CRC的有吸引力的治疗策略。

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