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

• Published in: The FEBS journal 2017-09, Vol.284 (18), p.3000-3017
• Main Authors: Wu, Lanfang, Han, Lingfei, Zhou, Chenfei, Wei, Wenfei, Chen, Xiaojing, Yi, Hongyan, Wu, Xiangguang, Bai, Xiangyang, Guo, Suiqun, Yu, Yanhong, Liang, Li, Wang, Wei
• Format: Article
• Language: English
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.14162

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.