Background: Cancer stem cells (CSCs) are a small subpopulation of cells within tumors
and play significant roles in tumorigenesis, metastasis, resistance to treatment, and relapse. They
are defined by self-renewal and multi-lineage differentiation, and aggressiveness. Epigenetic modifications,
including DNA methylation and acetylation, histone modifications, and non-coding.
RNAs (ncRNAs), are partly responsible for CSC potentials and are involved in the modification of
key components of crucial pathways such as Notch and Wnt signaling in breast cancer.
Objective: In this review, we present an overview of the pathways and epigenetic events that lead
to the transformation of mammary gland stem cells to breast CSCs (BCSCs). Based on the data presented
here, important pathways such as TGF-β/SMAD2 and Wnt/β-catenin and epigenetic modifications,
including histone modifications, DNA methylations, and microRNAs, play important roles
in BCSC formation and maintenance.
Conclusion: Epigenetic events can alter the expression of genes and functional RNAs, resulting in
tumor initiation and progression. Thus, a better understanding of epigenetic modifications involved
in BCSC maintenance signaling pathways may help to eliminate or suppress BCSCs and overcome
cancer by generating more effective and efficient therapeutic agents.