c-Ski activates cancer-associated fibroblasts to regulate breast cancer cell invasion.
c-Ski activates cancer-associated fibroblasts to regulate breast cancer cell invasion.
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DOI：
10.1016/j.molonc.2013.08.007
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发表时间：
2013-12
影响因子：
6.6
通讯作者：
Liu, Manran
中科院分区：
文献类型：
--
作者：
Wang, Liyang;Hou, Yixuan;Sung, Yan;Zhao, Liuyang;Tang, Xi;Hu, Ping;Yang, Jiajia;Zeng, Zongyue;Yang, Guanglun;Cui, Xiaojiang;Liu, Manran
c-Ski癌蛋白在某些肿瘤细胞中的异常表达已被证明与癌症的发展有关。然而，c-Ski在肿瘤微环境的癌症相关成纤维细胞（CAF）中的作用尚未被表征。在本研究中，我们发现c-Ski在来自乳腺癌微环境的CAF中高度表达，并且这种CAF相关的c-Ski表达与人类乳腺肿瘤的侵袭和转移相关。我们发现，c-Ski在永生化乳腺正常成纤维细胞（NF）中的过表达通过抑制p53从而上调NF中的SDF-1诱导向乳腺CAFs的转化。SDF-1处理或NF中p53敲低对NF的活化具有与c-Ski过表达类似的作用。与NF相比，c-Ski激活的CAFs显示出增加的增殖、迁移、侵袭和收缩。此外，c-Ski激活的CAF促进MDA-MB-231乳腺癌细胞的迁移和侵袭。我们的数据表明，c-Ski是激活CAFs的重要调节因子，并可能成为阻断乳腺癌进展的潜在治疗靶点。
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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影响因子：
11.2
作者：
Anderberg C;Li H;Fredriksson L;Andrae J;Betsholtz C;Li X;Eriksson U;Pietras K
通讯作者：
Pietras K
影响因子：
5.4
作者：
LI, Y;TURCK, CM;STAVNEZER, E
通讯作者：
STAVNEZER, E
影响因子：
4.6
作者：
Boone, Barbara;Haspeslagh, Marc;Brochez, Lieve
通讯作者：
Brochez, Lieve
影响因子：
5.3
作者：
Micke, P;Östman, A
通讯作者：
Östman, A
影响因子：
7.3
作者：
Franco OE;Shaw AK;Strand DW;Hayward SW
通讯作者：
Hayward SW