Metformin suppresses triple-negative breast cancer stem cells by targeting KLF5 for degradation
文献类型：期刊论文
| 作者 | Shi PG1,2; Liu WJ1,3; Zhang HL1; Wu YY1,2,6; Kong YJ1; Zhou ZM1; Wang CY6; Chen WL7; Tala4; Liu R1 |
| 刊名 | Cell Discovery
 |
| 出版日期 | 2017 |
| 卷号 | 3期号:X页码:e17010 |
| 关键词 | KLF5 metformin PKA stem cells triple-negative breast cancer |
| 通讯作者 | chenc@mail.kiz.ac.cn |
| 合作状况 | 其它 |
| 英文摘要 | Out of the breast cancer subtypes, triple-negative breast cancer (TNBC) has the poorest prognosis without effective targeted therapies. Metformin, a first-line drug for type 2 diabetes mellitus, was demonstrated to target breast cancer stem cells selectively. However, the efficiency and the mechanism of action of metformin in TNBC are unclear. In this study, we demonstrated that metformin decreased the percentage of TNBC stem cells partially through the downregulation of the expression of the stem cell transcription factor Krüppel-like factor 5 (KLF5) and its downstream target genes, such as Nanog and FGF-BP1, in TNBC cell lines. Metformin induced glycogen synthase kinase-3β (GSK3β)-mediated KLF5 protein phosphorylation and degradation through the inhibition of protein kinase A (PKA) activity in TNBC cells. Consistently, PKA activators increased the expression levels of KLF5. We observed a positive correlation between p-CREB, p-GSK3β, KLF5 and FGF-BP1 protein levels in human TNBC samples. These findings suggest that metformin suppresses TNBC stem cells partially through the PKA-GSK3β-KLF5 signaling pathway. |
| 收录类别 | SCI |
| 资助信息 | This study was supported by the National Nature Science Foundation of China (81325016 and U1602221 to CC, 81672639 to ZZ, U1502222, 81322038 and 81272930 to RL), the Yunnan Applied Basic Research Key Projects (2015FA027 to RL), the West Light Foundation of the Chinese Academy of Sciences (to RL) and the Youth Innovation Promotion Association and the Chinese Academy of Sciences (to RL). |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/11055]  |
| 专题 | 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 昆明动物研究所_肿瘤生物学 |
| 作者单位 | 1.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China 2.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China 3.Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China 4.State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China 5.School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, China 6.Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, China 7.Cancer Hospital, Kunming Medical University, Kunming, China |
| 推荐引用方式 GB/T 7714 | Shi PG,Liu WJ,Zhang HL,et al. Metformin suppresses triple-negative breast cancer stem cells by targeting KLF5 for degradation[J]. Cell Discovery,2017,3(X):e17010. |
| APA | Shi PG.,Liu WJ.,Zhang HL.,Wu YY.,Kong YJ.,...&Li FB.(2017).Metformin suppresses triple-negative breast cancer stem cells by targeting KLF5 for degradation.Cell Discovery,3(X),e17010. |
| MLA | Shi PG,et al."Metformin suppresses triple-negative breast cancer stem cells by targeting KLF5 for degradation".Cell Discovery 3.X(2017):e17010. |
入库方式： OAI收割
来源：昆明动物研究所
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