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

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. A signaling molecule implicated in nearly one-third of human cancers may help identify therapies for an aggressive type of breast cancer. Basal-type breast cancers are highly migratory and invasive, and are resistant to hormonal treatments effective against other breast cancers. However, the mechanism making basal-type cells so aggressive remained elusive. Su-Jae Lee from Hanyang University and co-workers in Korea investigated the role of Kirsten rat sarcoma viral oncogene homolog (KRAS), a small signaling molecule. Comparing basal-type and less invasive (luminal-type) cancer cells showed higher KRAS activity in the basal-type cells. Inserting a cancer-causing form of KRAS into normal breast cells made them migratory and invasive. Loss of KRAS made basal-type cancer cells less aggressive. KRAS appears to act as a critical switch in basal-type breast cancers, and shows promise as a therapeutic target