Original article from STEM CELLS
Targeting RSK Eliminates Tumor-Initiating Cells by Inactivating YB-1 in Triple-Negative Breast Cancers
Triple-negative breast cancer (TNBC) refers to any breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) or Her2/neu andtherefore does not respond to conventional therapeutic approaches. These tumours become resistant to chemotherapeutic agents and are prone to recurrence, which has been linked to the presence of high numbers of CD44+/CD24− tumour initiating cells (TICs) which are intrinsically resistant to traditional chemotherapy and radiotherapy (Creighton et al, Li et al and Philips et al). A further concern is that the percentage of TICs increases following chemotherapeutic treatment of breast cancers with agents such as paclitaxel (Creighton et al and Fillmore and Kuperwasser). This suggests that the targeting of CD44+ TICs may be of value to the treatment of TNBC. A previous study has shown that the transcription factor YB-1 can regulate the TIC phenotype in TNBC, increasing TIC marker (CD44 and CD49f (or ITGA6)) expression, mammosphere formation and drug resistance (To et al). YB-1 is phosphorylated and activated, leading to nuclear translocation and transcriptional activation, by the p90 ribosomal S6 kinases (RSK) (To et aland Stratford et al) suggesting that these kinases may be a viable therapeutic target for TNBC. Now, researchers from the laboratory of Sandra E. Dunn at the University of British Columbia, Vancouver, Canada have reported that blocking the activation of YB-1 via RSK inhibition could be an alternative approach to combating relapse by eliminating TICs present in TNBC (Stratford and Reipas et al).