Abstract
(1) Aim: In the present paper we analyzed the transcriptome of CSCs (Cancer Stem Cells), in order to find defining molecular processes of breast cancer. (2) Methods: We performed RNA-Seq from CSCs isolated from the basal cell line MDA-MB-468. Enriched processes and networks were studied using the IPA (Ingenuity Pathway Analysis) tool. Validation was performed with qRT-PCR and the analysis of relevant genes was evaluated by overexpression, flow cytometry and in vivo zebrafish studies. Finally, the clinical relevance of these results was assessed using reported cohorts. (3) Results: We found that CSCs presented marked differences from the non-CSCs, including enrichment in transduction cascades related to stemness, cellular growth, proliferation and apoptosis. Interestingly, CSCs overexpressed a module of co-regulated Chromosomal Passenger Proteins including BIRC5 (survivin), INCENP and AURKB. Overexpression of BIRC5 increased the number of CSCs, as assessed by in vitro and in vivo zebrafish xenotransplant analyses. Analysis of previously published cohorts showed that this co-regulated module was not only overexpressed in basal breast tumors but also associated with relapse-free and overall survival in these patients. (4) Conclusions: These results underline the importance of Cancer Stem Cells in breast cancer progression and point toward the possible use of chromosomal passenger proteins as prognostic factors.
Highlights
Breast cancer is the most commonly diagnosed cancer among women from both developing and developed countries and it remains one of the leading causes of death in women worldwide [1]
We analyzed the transcriptome of Breast Cancer Stem Cells (BCSCs) derived from the basal breast cancer cell line MDA-MB-468 in which we found enrichment in gene networks associated with several signaling cascades related to stemness
Among the regulated networks we found a novel module consisting of genes codifying for chromosomal passenger proteins, including BIRC5, INCENP and AURKB, which proved to be associated with relapse-free and overall survival in triple-negative breast tumors
Summary
Breast cancer is the most commonly diagnosed cancer among women from both developing and developed countries and it remains one of the leading causes of death in women worldwide [1]. Among the described molecular subtypes, patients with basal breast tumors present the poorest prognosis, with shorter metastasis-free and overall survival [2]. These tumors have a gene expression pattern very similar to mammary stem cells [3], and reciprocally, normal mammary stem cells overexpress a set of genes common to basal breast tumors [4]. We analyzed the transcriptome of BCSCs derived from the basal breast cancer cell line MDA-MB-468 in which we found enrichment in gene networks associated with several signaling cascades related to stemness. Among the regulated networks we found a novel module consisting of genes codifying for chromosomal passenger proteins, including BIRC5, INCENP and AURKB, which proved to be associated with relapse-free and overall survival in triple-negative breast tumors
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