Reduced DAPK1 Expression Promotes Stem Cell-Like Characteristics of Prostate Cancer Cells by Activating ZEB1 via Hippo/YAP Signaling Pathway

生物 河马信号通路 SOX2 CD44细胞 细胞生物学 干细胞 信号转导 癌症研究 前列腺癌 细胞 癌症干细胞 干细胞标记物 细胞生长 林28 基因敲除 癌症 细胞培养 转录因子 基因 生物化学 遗传学
作者
Shaojun Nong,Zhongqing Wei,Zhiwei Wang,Limin Ma,Yangbo Guan,Jian Ni
出处
期刊:Stem Cells and Development [Mary Ann Liebert]
卷期号:30 (18): 934-945 被引量:10
标识
DOI:10.1089/scd.2021.0043
摘要

Prostate cancer (PCa) is a malignant tumor that originates in the male genitourinary system. Downregulation of death-associated protein kinase 1 (DAPK1) is closely related to PCa. Little is known about the functional role of DAPK1 in regulating cancer stem cell (CSC)-like characteristics of PCa cells, and we have conducted research on this topic. Compared with tumor-adjacent normal tissues, DAPK1 was severely downregulated in tumor tissues of PCa patients. DAPK1 expression was also reduced in PCa cell lines with respect to that in normal prostate cells. Moreover, we sorted PCa-CSCs (PCa-CD133+ cells) from PCa cells. PCa-CD133+ cells also exhibited a reduced DAPK1 level and elevated levels of stem cell markers (CD44, OCT4, and SOX2). DAPK1 knockdown promoted sphere formation and enhanced the proportions of PCa-CD133+/PCa-CD133- cells. Inhibition of DAPK1 also accelerated migration and invasion of PCa-CD133+ cells. In addition, DAPK1 interacted with zinc finger E-box-binding homeobox-1 (ZEB1) and repressed ZEB1 expression in PCa-CD133+ cells. DAPK1 suppressed Hippo/YAP signaling pathway by interacting with ZEB1. Finally, we generated a tumor xenograft model to verify the effect of PCa-CD133+ cells following DAPK1 overexpression on tumor growth of PCa. DAPK1 overexpression inhibited tumor growth of PCa and repressed the expression of ZEB1, YAP, and TAZ in the tumor tissues of PCa mice. In conclusion, reduced DAPK1 expression promoted stem cell-like characteristics of PCa cells through activating ZEB1 via Hippo/YAP signaling pathway. Taken together, this work sheds lights on the potential of DAPK1 as a target for PCa therapeutics from bench to clinic.
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