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c-Ski activates cancer-associated fibroblasts to regulate breast cancer cell invasion

Wang, Liyang, Hou, Yixuan, Sun, Yan, Zhao, Liuyang, Tang, Xi, Hu, Ping, Yang, Jiajia, Zeng, Zongyue, Yang, Guanglun, Cui, Xiaojiang, Liu, Manran·2013·Molecular Oncology
DOI 10.1016/j.molonc.2013.08.007PMC PMC3864893
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Abstract

Aberrant expression of c‐Ski oncoprotein in some tumor cells has been shown to be associated with cancer development. However, the role of c‐Ski in cancer‐associated fibroblasts (CAFs) of tumor microenvironment has not been characterized. In the current study, we found that c‐Ski is highly expressed in CAFs derived from breast carcinoma microenvironment and this CAF‐associated c‐Ski expression is associated with invasion and metastasis of human breast tumors. We showed that c‐Ski overexpression in immortalized breast normal fibroblasts (NFs) induces conversion to breast CAFs by repressing p53 and thereby upregulating SDF‐1 in NFs. SDF‐1 treatment or p53 knockdown in NFs had similar effects on the activation of NFs as c‐Ski overexpression. The c‐Ski‐activated CAFs show increased proliferation, migration, invasion and contraction compared with NFs. Furthermore, c‐Ski‐activated CAFs facilitated the migration and invasion of MDA‐MB‐231 breast cancer cells. Our data suggest that c‐Ski is an important regulator in the activation of CAFs and may serve as a potential therapeutic target to block breast cancer progression.

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Metadata

Authors
Wang, L., Hou, Y., Sun, Y., Zhao, L., Tang, X., Hu, P., Yang, J., Zeng, Z., Yang, G., Cui, X., & Liu, M.
Venue
Molecular Oncology
Publisher
Wiley
Published
2013-08-27
Volume
7
Issue
6
Pages
1116-1128
ISSN
  • 1574-7891
  • 1878-0261
DOI
10.1016/j.molonc.2013.08.007
PMC
PMC3864893
Cited by
43
References
2
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Funders
  • National Natural Science Foundation of China (NSFC 81072147, NSFC 30940096)
  • Natural Science Foundation of Chongqing Science & Technology Commission, China (CSTC2010BB5099)
  • Doctoral Fund of Ministry of Education, China (20105503110001)
  • Scientific Research Foundation for the Returned Overseas Chinese Scholars, Ministry of Education, China ([2011]508)
  • Major Program of Chongqing Medical University (XBZD201006)
  • Scientific Research Foundation for the Returned Overseas Scholars of Chongqing Medical University
  • National Institutes of Health (R01CA151610)
  • Avon Foundation (02-2010-068)

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CoChat. (2026). Citation check: c-Ski activates cancer-associated fibroblasts to regulate breast cancer cell invasion. https://app.cochat.ai/papers/10.1016/j.molonc.2013.08.007
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Wang, L., Hou, Y., Sun, Y., Zhao, L., Tang, X., Hu, P., Yang, J., Zeng, Z., Yang, G., Cui, X., & Liu, M. (2013). c-Ski activates cancer-associated fibroblasts to regulate breast cancer cell invasion. Molecular Oncology. https://doi.org/10.1016/j.molonc.2013.08.007