上皮间质转化（EMT）是指极性上皮细胞在特定的生理或病理条件下转变为能活动的间质细胞，从而促进癌细胞的转移。上皮钙粘蛋白 (E-cadherin) 是一种在肿瘤细胞运动获得中发挥重要作用的蛋白质，是关键的 EMT 上皮标志物。本研究以E-钙粘蛋白为靶点，通过细胞内Western高通量筛选技术鉴定出一种具有潜在治疗功效的小分子化合物AW01178。该化合物在 mRNA 和蛋白质水平上诱导 E-cadherin 上调，并抑制体外乳腺癌细胞的 EMT 和体内转移。从机制上讲，AW01178 是一种新型苯甲酰胺组蛋白脱乙酰酶抑制剂 (HDACi)，主要针对 I 类组蛋白脱乙酰酶。 AW01178通过增强E-cadherin启动子区组蛋白H3的乙酰化水平，促进E-cadherin的转录和表达，从而抑制乳腺癌细胞的转移。集体研究结果支持了本研究中确定的新型 HDACi 化合物 AW01178 作为乳腺癌治疗药物的潜在用途，并强调了其对于未来开发 HDACi 结构作为抗癌药物的价值。

Epithelial-mesenchymal transition (EMT) refers to the transformation of polar epithelial cells into motile mesenchymal cells under specific physiological or pathological conditions, thus promoting the metastasis of cancer cells. Epithelial cadherin (E-cadherin) is a protein that plays an important role in the acquisition of tumor cell motility and serves as a key EMT epithelial marker. In the present study, AW01178, a small-molecule compound with potential therapeutic efficacy, was identified via in-cell Western high-throughput screening technology using E-cadherin as the target. The compound induced the upregulation of E-cadherin at both mRNA and protein levels and inhibited the EMT of breast cancer cells in vitro as well as metastasis in vivo. Mechanistically, AW01178 is a novel benzacetamide histone deacetylase inhibitor (HDACi) mainly targeting class I histone deacetylases. AW01178 promoted the transcription and expression of E-cadherin through enhancing the acetylation level of histone H3 in the E-cadherin promoter region, thereby inhibiting the metastasis of breast cancer cells. The collective findings support the potential utility of the novel HDACi compound identified in this study, AW01178, as a therapeutic drug for breast cancer and highlight its value for the future development of HDACi structures as anticancer drugs.