Kim Rae-Kwon, Suh Yongjoon, Yoo Ki-Chun, Cui Yan-Hong, Kim Hyeonmi, Kim Min-Jung, Gyu Kim In, Lee Su-Jae
Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, Korea.
Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Exp Mol Med. 2015 Jan 30;47(1):e137. doi: 10.1038/emm.2014.99.
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.
基底样乳腺癌是最具侵袭性和致命性的乳腺癌亚型之一，具有与间充质特征相关的高转移能力。然而，基底样乳腺癌细胞间充质表型维持的分子机制仍不清楚。在此，我们报告KRAS是基底样乳腺癌细胞间充质特征维持的关键调节因子。与管腔型相比，KRAS在基底样乳腺癌细胞中优先被激活。通过KRAS的缺失和过表达，我们发现KRAS对于通过SLUG表达维持间充质表型和转移能力是必要且充分的。综上所述，本研究表明KRAS是与乳腺癌细胞间充质特征相关的转移行为的关键调节因子，这意味着基底样乳腺癌有一个新的治疗靶点。
