Abstract
Cancer stem cells (CSCs) are crucial mediators of tumor growth, metastasis, therapy resistance, and recurrence in a broad variety of human cancers. Although their biology is increasingly investigated within the distinct types of cancer, direct comparisons of CSCs from different tumor types allowing comprehensive mechanistic insights are rarely assessed. In the present study, we isolated CSCs from endometrioid carcinomas, glioblastoma multiforme as well as adenocarcinomas of lung and prostate and assessed their global transcriptomes using full-length cDNA nanopore sequencing. Despite the expression of common CSC markers, principal component analysis showed a distinct separation of the CSC populations into three clusters independent of the specific type of tumor. However, GO-term and KEGG pathway enrichment analysis revealed upregulated genes related to ribosomal biosynthesis, the mitochondrion, oxidative phosphorylation, and glycolytic pathways, as well as the proteasome, suggesting a great extent of metabolic flexibility in CSCs. Interestingly, the GO term "NF-kB binding" was likewise found to be elevated in all investigated CSC populations. In summary, we here provide evidence for high global transcriptional similarities between CSCs from various tumors, which particularly share upregulated gene expression associated with mitochondrial and ribosomal activity. Our findings may build the basis for identifying novel therapeutic strategies targeting CSCs.
Highlights
Cancer stem cells (CSCs) are increasingly noticed to initiate tumor growth and to drive metastasis and tumor recurrence in a broad range of human cancers.Within the highly heterogeneous tumor cell mass, cancer stem cell (CSC) represent only a small subpopulation [2], but possess stem-like properties like self-renewal, asymmetric division and multi-lineage differentiation [4,5,6,7]
methylguanine-DNA methyltransferase (MGMT) promoter methylation status differed between the three donors, as glioblastomas of the donors of glioblastoma stem-like cells a (GSCs_a) and glioblastoma stem-like cells b (GSCs_b) depicted MGMT promoter methylation in contrast to the glioblastoma of donor GSCs_c
Among the enriched genes relevant for ribosome biosynthesis, we found distinct genes been the enriched genes relevant for ribosome biosynthesis, we found distinct genes been highly expressed in GSCs_b (Figure 6A), while prostate cancer stem-like cells b (PCSCs_b) and endometrioid cancer stem-like cells c (ECSCs_c) showed other genes highly expressed in GSCs_b (Figure 6A), while PCSCs_b and ECSCs_c showed other upregulated for ribosome biosynthesis (Figure 6B)
Summary
Cancer stem cells (CSCs) are increasingly noticed to initiate tumor growth and to drive metastasis and tumor recurrence in a broad range of human cancers (reviewed in [1]).Within the highly heterogeneous tumor cell mass, CSCs represent only a small subpopulation [2] (reviewed in [3]), but possess stem-like properties like self-renewal, asymmetric division and multi-lineage differentiation [4,5,6,7] (reviewed in [1]). CSCs remain hidden in the body of the patients until their reactivation by various stimuli leads to the regeneration of the tumor or to the formation of metastasis [8]. These characteristics facilitate the role of CSCs as major drivers of tumor formation and progression. We isolated CSCs from endometrioid carcinomas, glioblastoma multiforme, as well as adenocarcinomas of lung and prostate, and assessed their global transcriptomes by nanopore RNA sequencing (RNA-Seq) to identify such potential common regulators and mechanisms
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