Activation of KRAS promotes the mesenchymal features of basal-type breast cancer

被引:69
作者
Kim, Rae-Kwon [1 ]
Suh, Yongjoon [1 ]
Yoo, Ki-Chun [1 ]
Cui, Yan-Hong [1 ]
Kim, Hyeonmi [1 ]
Kim, Min-Jung [2 ]
Kim, In Gyu [3 ]
Lee, Su-Jae [1 ]
机构
[1] Hanyang Univ, Dept Life Sci, Res Inst Nat Sci, Seoul 133791, South Korea
[2] Korea Inst Radiol & Med Sci, Natl Radiat Emergency Med Ctr, Lab Radiat Exposure & Therapeut, Seoul, South Korea
[3] Korea Atom Energy Res Inst, Dept Radiat Biol, Environm Radiat Res Grp, Taejon, South Korea
基金
新加坡国家研究基金会;
关键词
GENE-EXPRESSION; RAS ONCOGENES; SLUG; TRANSITIONS; PROGRESSION; MUTATIONS; PHENOTYPE; SURVIVAL; VARIANT;
D O I
10.1038/emm.2014.99
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Basal-type breast cancers are among the most aggressive and deadly breast cancer subtypes, displaying a high metastatic ability associated with mesenchymal features. However, the molecular mechanisms underlying the maintenance of mesenchymal phenotypes of basal-type breast cancer cells remain obscure. Here, we report that KRAS is a critical regulator for the maintenance of mesenchymal features in basal-type breast cancer cells. KRAS is preferentially activated in basal-type breast cancer cells as compared with luminal type. By loss and gain of KRAS, we found that KRAS is necessary and sufficient for the maintenance of mesenchymal phenotypes and metastatic ability through SLUG expression. Taken together, this study demonstrates that KRAS is a critical regulator for the metastatic behavior associated with mesenchymal features of breast cancer cells, implicating a novel therapeutic target for basal-type breast cancer.
引用
收藏
页码:e137 / e137
页数:9
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