New breast cancer stem cell study
Despite advances in diagnosis and treatment, breast cancer is associated with increased relapse. This is mainly from intrinsic and acquired resistance to endocrine therapy, pointing towards the presence of a subpopulation of cancer stem cells (CSCs). CSCs are believed to be responsible for cancer emergence and maintenance as they have the capacity to self-renew. Emerging evidence underscores a role for epigenetic mechanisms in CSC biology such as DNA methylation and post-translational histone modifications. Epigenetics refers to heritable changes in gene expression that do not involve changes in the underlying DNA sequence. Scientists on the EU-funded EPIGBRCASTEM (The epigenome of breast cancer stem cells) project set out to elucidate the epigenetics governing breast CSCs and develop effective treatments that specifically target these cells. The work was based on recent studies that underscore a role for histone lysine demethylases as important players in the epigenetic control of cancer development and maintenance. Project researchers studied the histone demethylase LSD1 known for its involvement in embryonic stem cell pluripotency as well in leukaemia and hepatic cancer. In leukaemia, LSD1 maintains stem cell self-renewal and prohibits commitment to other lineages. Researchers developed an in vitro system for studying epigenetic mechanisms in breast CSCs and for testing epigenetic drugs. They observed that pharmacological inhibition of LSD1 diminished self-renewal capacity and decreased CSC population in breast cancer. Elucidation of the gene networks regulated by LSD1 will unveil novel therapeutic targets for breast cancer treatment. Collectively, the EPIGBRCASTEM findings indicate that LSD1 is important for the maintenance of the stem-like characteristics of breast CSCs. Apart from important knowledge on breast cancer tumourigenesis, the study results unveil novel targets for therapeutic intervention.
Keywords
Breast cancer, stem cell, cancer stem cell, epigenetics, LSD1
