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Although many breast cancer therapies show initial success in the treatment of the primary tumour, they often fail to eliminate a sub-population of cells known as cancer stem cells (CSCs). These cells are recognised for their self-renewal properties and for their capacity for differentiation often leading to chemo/radio-resistance. The antiviral drug Efavirenz has been shown to be effective in eliminating triple-negative breast cancer cells, and here we examine its effect on breast CSCs. The effects of Efavirenz on CSCs for several breast cancer cell lines were investigated by examining cellular changes upon drug treatment, including CSC numbers, morphology, RNA/microRNA expression and levels of epithelial/mesenchymal CSC subtypes. Efavirenz treatment resulted in a decrease in the size and number of tumorspheres and a reduction in epithelial-type CSC levels, but an increase in mesenchymal-type CSCs. Efavirenz caused upregulation of several CSC-related genes as well as miR-21 , a CSC marker and miR-182 , a CSC suppressor gene. We conclude that Efavirenz alters the phenotype and expression of key genes in breast CSCs, which has important potential therapeutic implications.

Purpose: In contrast to hormone receptor driven breast cancer, patients presenting with triple-negative breast cancer (TNBC) often have limited drug treatment options. Efavirenz, a non-nucleoside reverse transcriptase (RT) inhibitor targets abnormally overexpressed long interspersed nuclear element 1 (LINE-1) RT and has been shown to be a promising anticancer agent for treating prostate and pancreatic cancers. However, its effectiveness in treating patients with TNBC has not been comprehensively examined., Methods: In this study, the effect of Efavirenz on several TNBC cell lines was investigated by examining several cellular characteristics including viability, cell division and death, changes in cell morphology as well as the expression of LINE-1., Results: The results show that in a range of TNBC cell lines, Efavirenz causes cell death, retards cell proliferation and changes cell morphology to an epithelial-like phenotype. In addition, it is the first time that a whole-genome RNA sequence analysis has identified the fatty acid metabolism pathway as a key regulator in this Efavirenz-induced anticancer process., Conclusion: In summary, we propose Efavirenz is a potential anti-TNBC drug and that its mode of action can be linked to the fatty acid metabolism pathway.

Ribosome biogenesis takes place in the nucleolus, the size of which is often coordinated with cell growth and development. However, how metazoans control nucleolar size remains largely unknown. Caenorhabditis elegans provides a good model to address this question owing to distinct tissue distribution of nucleolar sizes and a mutant, ncl-1, which exhibits larger nucleoli than wild-type worms. Here, through a series of loss-of-function analyses, we report that the nucleolar size is regulated by a circuitry composed of microRNA let-7, translation repressor NCL-1, and a major nucleolar pre-rRNA processing protein FIB-1/fibrillarin. In cooperation with RNA binding proteins PUF and NOS, NCL-1 suppressed the translation of FIB-1/fibrillarin, while let-7 targeted the 3'UTR of ncl-1 and inhibited its expression. Consequently, the abundance of FIB-1 is tightly controlled and correlated with the nucleolar size. Together, our findings highlight a novel genetic cascade by which post-transcriptional regulators interplay in developmental control of nucleolar size and function.