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
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 b...
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| Published in | The FEBS journal Vol. 284; no. 18; pp. 3000 - 3017 |
|---|---|
| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
01.09.2017
|
| Online Access | Get full text |
| ISSN | 1742-464X 1742-4658 |
| DOI | 10.1111/febs.14162 |
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| Abstract | 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. |
|---|---|
| AbstractList | 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. |
| Author | Wu, Xiangguang Han, Lingfei Chen, Xiaojing Yi, Hongyan Guo, Suiqun Liang, Li Wu, Lanfang Wang, Wei Bai, Xiangyang Yu, Yanhong Zhou, Chenfei Wei, Wenfei |
| Author_xml | – sequence: 1 givenname: Lanfang surname: Wu fullname: Wu, Lanfang organization: Department of Obstetrics and Gynecology The First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong, China, Department of Obstetrics and Gynecology The Third Affiliated Hospital of Southern Medical University Guangzhou, Guangdong China – sequence: 2 givenname: Lingfei surname: Han fullname: Han, Lingfei organization: Department of Minimally Invasive Gynecologic Surgery Shanghai First Maternity and Infant Hospital Tongji University School of Medicine Shanghai China – sequence: 3 givenname: Chenfei surname: Zhou fullname: Zhou, Chenfei organization: Department of Obstetrics and Gynecology Nanfang Hospital, Southern Medical University Guangzhou, Guangdong China – sequence: 4 givenname: Wenfei surname: Wei fullname: Wei, Wenfei organization: Department of Obstetrics and Gynecology Nanfang Hospital, Southern Medical University Guangzhou, Guangdong China – sequence: 5 givenname: Xiaojing surname: Chen fullname: Chen, Xiaojing organization: Department of Obstetrics and Gynecology Nanfang Hospital, Southern Medical University Guangzhou, Guangdong China – sequence: 6 givenname: Hongyan surname: Yi fullname: Yi, Hongyan organization: Department of Obstetrics and Gynecology Nanfang Hospital, Southern Medical University Guangzhou, Guangdong China – sequence: 7 givenname: Xiangguang surname: Wu fullname: Wu, Xiangguang organization: Department of Obstetrics and Gynecology Nanfang Hospital, Southern Medical University Guangzhou, Guangdong China – sequence: 8 givenname: Xiangyang surname: Bai fullname: Bai, Xiangyang organization: Department of Obstetrics and Gynecology Nanfang Hospital, Southern Medical University Guangzhou, Guangdong China – sequence: 9 givenname: Suiqun surname: Guo fullname: Guo, Suiqun organization: Department of Obstetrics and Gynecology The Third Affiliated Hospital of Southern Medical University Guangzhou, Guangdong China – sequence: 10 givenname: Yanhong surname: Yu fullname: Yu, Yanhong organization: Department of Obstetrics and Gynecology Nanfang Hospital, Southern Medical University Guangzhou, Guangdong China – sequence: 11 givenname: Li surname: Liang fullname: Liang, Li organization: Department of Pathology Nanfang Hospital, Southern Medical University Guangzhou, Guangdong, China – sequence: 12 givenname: Wei orcidid: 0000-0002-3422-0402 surname: Wang fullname: Wang, Wei organization: Department of Obstetrics and Gynecology The First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong, China, Department of Obstetrics and Gynecology Nanfang Hospital, Southern Medical University Guangzhou, Guangdong China |
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| Title | 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 |
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