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TGF ‐β1‐induced CK 17 enhances cancer stem cell‐like properties rather than EMT in promoting cervical cancer metastasis via the ERK 1/2‐ MZF 1 signaling pathway
Author(s) -
Wu Lanfang,
Han Lingfei,
Zhou Chenfei,
Wei Wenfei,
Chen Xiaojing,
Yi Hongyan,
Wu Xiangguang,
Bai Xiangyang,
Guo Suiqun,
Yu Yanhong,
Liang Li,
Wang Wei
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14162
Subject(s) - metastasis , cancer research , gene silencing , epithelial–mesenchymal transition , cancer stem cell , signal transduction , mapk/erk pathway , transforming growth factor , chemistry , biology , cancer , microbiology and biotechnology , stem cell , biochemistry , gene , genetics
Tumor metastasis remains a major obstacle for improving overall cancer survival in cervical cancer ( CC ), which may be due to the existence of tumor microenvironment‐related cancer stem cells ( CSC s) and epithelial–mesenchymal transition ( EMT ). The mechanism underlying these processes needs to be further elucidated. Here, we report that TGF ‐β1, one of the key microenvironmental stimuli, can enhance CSC characteristics, facilitate the EMT , and induce CK 17. Silencing CK 17 expression attenuated CSC ‐like properties without affecting the EMT markers induced by TGF ‐β1, whereas forced overexpression of CK 17 promoted lymphatic metastasis in vivo even without EMT inducement. Inhibitors of ERK 1/2 signaling drastically decreased the induction of CK 17 mediated by TGF ‐β1. By combined computational and experimental approaches, we identified and validated that MZF 1 was a key transcription factor binding to the promoter of CK 17. Taken together, these results demonstrate that CK 17 induced by the TGF ‐β1‐ ERK 1/2‐ MZF 1 signaling pathway facilitates metastasis by promoting the acquisition of CSC properties rather than by inducing the EMT process in CC , suggesting that this CK 17‐related signaling pathway might be a suitable target for the development of therapy for CC metastasis.