Harmine inhibits breast cancer cell migration and invasion by inducing the degradation of Twist1.
Harmine inhibits breast cancer cell migration and invasion by inducing the degradation of Twist1.
复制标题
毒碱通过诱导Twist1的降解抑制乳腺癌细胞的迁移和侵袭。
DOI：
10.1371/journal.pone.0247652
复制
发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Nafie E;Lolarga J;Lam B;Guo J;Abdollahzadeh E;Rodriguez S;Glackin C;Liu J
乳腺癌是美国癌症相关死亡的主要原因。乳腺癌患者的大多数死亡 (90%) 是由侵袭和转移引起的，这两个特征与上皮间质转化 (EMT) 相关。 Twist1是促进EMT的关键转录因子，可导致细胞迁移、侵袭、癌症转移和治疗耐药。 Harmine 是一种在多种植物中发现的 β-咔啉生物碱，最近被证明能够诱导非小细胞肺癌 (NSCLC) 细胞中 Twist 家族 BHLH 转录因子 1 (Twist1) 的降解。在这项研究中，我们证明去氢骆驼蓬碱可以以剂量依赖性方式抑制人和小鼠乳腺癌细胞的迁移和侵袭。进一步的研究表明，这种抑制很可能是通过诱导蛋白酶体依赖性 Twist1 降解来实现的。在测试浓度下，去氢骆驼蓬碱并没有显着影响细胞的活力，这表明它对癌细胞迁移和侵袭的抑制在很大程度上与其细胞毒性无关，而是由于它能够影响 EMT 调节因子（例如 Twist1）。这一结果可能有助于开发针对 Twist1 的治疗转移性乳腺癌的策略，因为 Twist1 在转移性乳腺癌细胞中高水平表达，但在正常细胞中不表达。
Breast cancer is the leading cause of cancer-related deaths in the United States. The majority of deaths (90%) in breast cancer patients is caused by invasion and metastasis–two features related to the epithelial-to-mesenchymal transition (EMT). Twist1 is a key transcription factor that promotes the EMT, which leads to cell migration, invasion, cancer metastasis, and therapeutic resistance. Harmine is a beta-carboline alkaloid found in a variety of plants and was recently shown to be able to induce degradation of Twist Family BHLH Transcription Factor 1 (Twist1) in non-small cell lung cancer cells (NSCLC). In this study, we show that harmine can inhibit migration and invasion of both human and mouse breast cancer cells in a dose-dependent manner. Further study shows that this inhibition is most likely achieved by inducing a proteasome-dependent Twist1 degradation. At the concentrations tested, harmine did not affect the viability of cells significantly, suggesting that its inhibition of cancer cell migration and invasion is largely independent of its cytotoxicity, but due to its ability to affect regulators of EMT such as Twist1. This result may facilitate the development of strategies that target Twist1 to treat metastatic breast cancer, as Twist1 is expressed at a high level in metastatic breast cancer cells but not in normal cells.
登录
查看更多内容
影响因子：
2.7
作者：
Fan C;Prat A;Parker JS;Liu Y;Carey LA;Troester MA;Perou CM
通讯作者：
Perou CM
影响因子：
5.2
作者：
Ding, Yu;He, Jinrong;Peng, Caixia
通讯作者：
Peng, Caixia
影响因子：
50.3
作者：
Ansieau, Stephane;Bastid, Jeremy;Puisieux, Alain
通讯作者：
Puisieux, Alain
DOI：
10.1016/j.bbrc.2005.10.121
发表时间：
2005-12-23
影响因子：
3.1
作者：
Cao, RH;Peng, WL;Xu, AL
通讯作者：
Xu, AL
影响因子：
--
作者：
Wang, Wen-Shuang;Yang, Xing-Sheng;Hou, Jian-Qing
通讯作者：
Hou, Jian-Qing