Abstract
Breast cancer is the most common malignancy in women worldwide and can be categorized into several subtypes according to histopathological parameters or genomic signatures. Such heterogeneity of breast cancer can arise from the reactivation of mammary stem cells in situ during tumorigenesis. Moreover, different breast cancer subtypes exhibit varieties of cancer incidence, therapeutic response, and patient prognosis, suggesting that a specific therapeutic protocol is required for each breast cancer subtype. Recent studies using molecular and cellular assays identified a link between specific genetic/epigenetic alterations and distinct cells of origin of breast cancer subtypes. These alterations include oncogenes, tumor suppressor genes, and cell-lineage determinants, which can induce cell reprogramming (dedifferentiation and transdifferentiation) among two lineage-committed mammary epithelial cells, namely basal and luminal cells. The interconversion of cell states through cell reprogramming into the intermediates of mammary stem cells can give rise to heterogeneous breast cancers that complicate effective therapies of breast cancer. A better understanding of mechanisms underlying cell reprogramming in breast cancer can help in not only elucidating tumorigenesis but also developing therapeutics for breast cancer. This review introduces recent findings on cancer gene-mediated cell reprogramming in breast cancer and discusses the therapeutic potential of targeting cell reprogramming.
Highlights
Embryonic stem cells (ESCs) are pluripotent stem cells that can differentiate into three germ layers: endoderm, mesoderm, and ectoderm
These results demonstrate that the PIK3CAH1047R mutation can initiate heterogeneous breast cancers by triggering the mammary stem cells (MaSCs) genetic program in differentiated basal cells (BCs) and luminal cells (LCs), providing new insights into the development of therapeutic strategies for phosphatidylinositol 3-kinase (PI3K)-related breast cancers
Poli et al [38] reported that MYC acts as an oncogenic reprogramming factor to convert TERT-immortalized human mammary epithelial cells and luminal breast cancer cells into the basal/stem cell-like state and gives rise to tumor-initiating cells (TICs) favoring the onset of mammary tumorigenesis
Summary
Embryonic stem cells (ESCs) are pluripotent stem cells that can differentiate into three germ layers: endoderm, mesoderm, and ectoderm. Takahashi and Yamanaka [1] introduced a cell reprogramming method that utilizes a combination of four TFs, namely OCT4, SOX2, KLF4, and MYC (OSKM), to convert differentiated fibroblasts back to an ESC-like state; the resulting cells are called induced pluripotent stem cells (iPSCs). This cell reprogramming method was proven to be successful in numerous cell types with various differentiation statuses and was applied in many research fields, including cancer research. A better understanding of cell reprogramming mechanisms in breast cancer can be helpful to unveil the potential therapeutic strategy to target different subtypes of breast cancer
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