Downregulation of DAPK1 promotes the stemness of cancer stem cells and EMT process by activating ZEB1 in colorectal cancer
Downregulation of DAPK1 promotes the stemness of cancer stem cells and EMT process by activating ZEB1 in colorectal cancer
复制标题
DAPK1的下调通过激活结直肠癌中的ZEB1促进癌症干细胞的干细胞性和EMT过程。
DOI：
10.1007/s00109-018-1716-8
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发表时间：
2019-01-01
影响因子：
4.7
通讯作者：
Shu, Xiaogang
中科院分区：
文献类型：
--
作者：
Yuan, Wenzheng;Ji, Jintong;Shu, Xiaogang
Cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) play an important role in the metastasis and chemoresistance in the context of colorectal cancer (CRC). Downregulation of death associated protein kinase 1 (DAPK1) may promote metastasis and chemoresistance of cancer cells through various mechanisms. However, the association between DAPK1 and CSCs or EMT has not been explored. In this study, we demonstrated that DAPK1 was associated with elevated stemness of CSCs in patients with CRC. Silencing of DAPK1 in CRC cell lines promoted the metastasis and chemoresistance due to increased stemness of CSCs and enhanced mesenchymal phenotype, an effect that was mediated via activation of the transcription factor, zinc finger E-box binding homeobox 1 (ZEB1). Blockade of this signaling pathway attenuated the stemness of CSCsand rescued the EMT process. DAPK1-ZEB1 may lie at the interface of TGF- and WNT pathways and participate in both CSCs and EMT process. Targeted therapies aimed at DAPK1-ZEB1 pathway may inhibit the chemoresistance and metastasis of CRC.Key messagesDownregulation of DAPK1 promotes chemoresistance and metastasis of CRC.Inhibition of DAPK1 promotes the stemness of cancer stem cells and EMT process.DAPK1-ZEB1 may lie at the interface of TGF- and WNT pathways.DAPK1-ZEB1 participates in both CSCs and EMT process.
