Cancer Stem Cell Dormancy and Epigenetic Regulation

JI Program: Cancer/Precision Health

Metastasis is the leading cause of cancer-related deaths worldwide. Recent studies show that metastatic cells can remain dormant and untreatable for long periods of time before generating metastases. The metastasis-initiating cells (MICs), in contrast to non-metastasis cells, are strongly influenced by specific types of metabolism and their derived metabolites. Metabolic and epigenetic rewiring are emerging as hallmarks of tumor progression and metastasis. The metabolic changes lead to alteration of cellular pools for SAM/SAH, α-ketoglutarate (α-KG), acetyl-CoA and short chain acyl-CoA, which in turn regulate covalent modification of histones and DNA for transcription activation and/or repression. These changes provide cancer cells with building blocks for anabolic needs and fulfills increased energy demands. This grant aims to understand interplay between cellular metabolic and epigenetic pathways in breast cancer and gain insights into MIC vulnerability and potential anti-metastatic therapies. We are particularly interested in the role of the histone acetylation/acylation MOF-YEAST4-CDYL axis, which is frequently dysregulated in breast cancers with poor prognosis.