Nuclear Receptor-Mediated Metabolic Reprogramming and the Impact on HR+ Breast Cancer

Abstract

Metabolic reprogramming enables cancer cells to adapt to the changing microenvironment in order to maintain metabolic energy and to provide the necessary biological macromolecules required for cell growth and tumor progression. While changes in tumor metabolism have been long recognized as a hallmark of cancer, recent advances have begun to delineate the mechanisms that modulate metabolic pathways and the consequence of altered signaling on tumorigenesis. This is particularly evident in hormone receptor positive (HR+) breast cancers which account for approximately 70% of breast cancer cases. Emerging evidence indicates that HR+ breast tumors are dependent on multiple metabolic processes for tumor progression, metastasis, and therapeutic resistance and that changes in metabolic programs are driven, in part, by a number of key nuclear receptors including hormone-dependent signaling. In this review, we discuss the mechanisms and impact of hormone receptor mediated metabolic reprogramming on HR+ breast cancer genesis and progression as well as the therapeutic implications of these metabolic processes in this disease.

Keywords: breast cancer; endocrine resistance; estrogen receptor; luminal; metabolic reprogramming; nuclear receptors.

Figure 1

Schematic representation of the crosstalk between cancer-associated major metabolic pathways altered in HR+ breast cancer.

Figure 2

Dynamic changes in major metabolic pathways by ER in sensitive and resistant breast cancer. Upregulated genes are shown in red and downregulated in blue.