Open Accessc‐Ski activates cancer‐associated fibroblasts to regulate breast cancer cell invasion
Author(s) -
Wang Liyang,
Hou Yixuan,
Sun Yan,
Zhao Liuyang,
Tang Xi,
Hu Ping,
Yang Jiajia,
Zeng Zongyue,
Yang Guanglun,
Cui Xiaojiang,
Liu Manran
Publication year - 2013
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2013.08.007
Subject(s) - cancer associated fibroblasts , cancer research , gene knockdown , metastasis , tumor microenvironment , breast cancer , cancer cell , tumor progression , cancer , cell migration , biology , cell growth , chemistry , medicine , cell , cell culture , tumor cells , genetics
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.