Dissecting the Origin of Breast Cancer Subtype Stem Cell and the Potential Mechanism of Malignant Transformation

Abstract

BackgroundBreast cancer is the most common incident form of cancer in women including different subtypes. Cancer stem cells (CSCs) have been confirmed to exist in breast cancer. But the research on the origin of breast cancer subtype stem cells (BCSSCs) is still inadequate.MethodsWe identified the putative origin cells of BCSSCs through comparing gene signatures between BCSSCs and normal mammary cells from multiple perspectives: common signature, expression consistency, functional similarity and shortest path length. First, the potential origin cells were ranked according to these measures separately. Then Q statistic was employed to combine all rank lists into a unique list for each subtype, to prioritize the origin cells for each BCSSC. Next, we identified origin-related gene modules through integrating functional interaction network with differentially expressed genes. Finally, transcription factors of significant gene modules were predicted by MatchTM.ResultsThe results showed that Luminal A CSC was most relevant to luminal progenitor cell or mature luminal cell; luminal B and HER2 CSC were most relevant to bipotent-enriched progenitor cell; basal-like CSC was most relevant to bipotent-enriched progenitor cell or mature luminal cell. Network modules analysis revealed genes related to mitochondrial respiratory chain (MRC) were significantly dysregulated during the origin of luminal B CSC. In addition, SOX10 emerged as a key regulator of MRC.ConclusionsOur study supports substantive evidence for the possible origin of four kinds of BCSSCs. Dysfunction of MRC may contribute to the origin of luminal B CSC. These findings may have important implications to treat and prevent breast cancer.

Breast cancer and Flammer syndrome: any symptoms in common for prediction, prevention and personalised medical approach?

“…BFeeling inadequately cold^may be interpreted in two ways. First, the heat production is not effective enough to maintain the physiologic body temperature, and the systemic mitochondrial dysfunction and DNA damage/misguided repair have been proposed as implemented in the BC pathology [28,29]. The second interpretation is the fever or fever-like conditions with excessive chill attacks regulated by proinflammatory cytokines, the expression profiles of which are frequently altered in cancer patients [30].…”

Concise Reviews: Cancer Stem Cell Targeted Therapies: Toward Clinical Success

“…These BCSCs were able to recapitulate the cellular heterogeneity of the original tumor and remained tumorigenic after multiple rounds of transplantation, suggesting this population contains the self‐renewal and differentiation properties of normal stem cells . Multiple theories exist regarding the origin of BCSCs including the accumulation of mutations that transform normal stem cells to CSCs , the “misplacement” of normal tissue stem cells that do not undergo transformation into connective tissue stroma , failure of the mitochondrial respiratory chain resulting in transformation , or the acquired phenotype of increased quiescence and stemness via alteration of DNA repair or other signaling pathways . Consistent with CSC characterization, a number of signaling pathways have been associated with the therapy resistance phenotype of BCSCs including Notch, Hedgehog, and Wnt which promote apoptosis evasion, maintenance of a stem cell niche, and increased invasion capacity .…”

Feeling cold and other underestimated symptoms in breast cancer: anecdotes or individual profiles for advanced patient stratification?

“…Maintaining thermal comfort is energetically costly [33] that requires well-organised energy supply by concerted mitochondrial cooperation at molecular and cellular levels. To this end, dysfunction of the mitochondrial respiratory chain has been demonstrated in BC cells [34]. Further, linked to the oxidative stress mechanisms, a systemic mitochondrial dysfunction and DNA damage/misguided repair have been proposed as implemented in the BC pathology [35].…”