三阴性乳腺癌
膜联蛋白A2
乳腺癌
癌症研究
化学
癌症
转移
半胱氨酸
膜联蛋白
生物
生物化学
内科学
医学
体外
酶
作者
Mingming Wei,Yunyun Zhou,Chong Li,Yuyu Yang,Tongtong Liu,Yulin Liu,Wei Yue,Ning Liu,Shuangwei Liu,Qianqian Wang,Sheng Cao,Yue Sun,Pengzhen Sheng,Lü Cheng,Cheng Yang,Xiang Liu,Guang Yang
标识
DOI:10.1021/acs.jmedchem.1c00267
摘要
Triple-negative breast cancer (TNBC) has been considered the most aggressive and mortal breast cancer. Thus far, it remains an important challenge to develop TNBC targeted therapy. As revealed from numerous recent studies, ANXA2 may be a potential target to treat TNBC. In the present study, a natural product 5α-epoxyalantolactone (5α-EAL) was discovered as an anti-breast cancer stem cells (BCSCs) lead compound. Furthermore, 5α-EAL was found to be able to notably suppress the function of ANXA2 by covalently targeting cysteine 9 (Cys9) of ANXA2. To the best of our knowledge, 5α-EAL was recognized as the first small molecule functional inhibitor of ANXA2. It could significantly inhibit the formation of the heterotetrameric complex of ANXA2 and S100A10, which is capable of transporting E-cadherin (E-Ca) to the membrane. The above findings may be used as a possible strategy to develop novel anti-TNBC therapies targeting ANXA2.
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