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Updated: Apr 1, 2026
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Estrogen-related receptor alpha and cancer: axis of evil
1a Orphan Nuclear Receptors Laboratory, Department of Biochemistry, St. Edmund's College , Shillong , India.
Abstract:
Cancer is perhaps the fastest growing non-communicable disease in the human population worldwide. Although the molecular mechanism of cancer initiation and progression is known to some extent, however, the majority of pathways responsible for its onset, development and progression are largely unknown. Many members of the nuclear receptors (NRs) superfamily of transcriptional factors have key roles in cancer. Estrogen-related receptor alpha (ERRα) is one of the members of the NR superfamily and studies have linked it with a wide variety of cancers. In endocrine-related cancers such as breast cancer, ERRα regulates a number of target genes directing cell proliferation and growth independent of estrogen receptor alpha (ERα). Knockdown of ERRα in a number of cancer tissues and cell lines significantly reduced tumor growth and malignancy indicating dependence on ERRα activity. The pro-angiogenesis factor vascular endothelial growth factor expression has been shown to be regulated by ERRα and has implications in several types of cancer. The effect of ERRα on cancers seems to be multipronged via regulation of cell cycle regulators, osteopontin, hypoxia inducible factor-1 as well as several energy metabolism genes that are part of glycolysis, TCA cycle, lipogenesis, etc., providing a metabolic twist to cancer. In this article, the action of ERRα on various types of cancers including new developments in this field shall be reviewed.
Insights
Estrogen-related receptor alpha (ERRα) drives cancer growth by regulating cell proliferation, angiogenesis, and metabolism. Targeting ERRα shows promise in reducing tumor growth and malignancy across various cancers.
Area of Science:
- Molecular Biology
- Oncology
- Endocrinology
Background:
- Cancer is a rapidly growing non-communicable disease with incompletely understood molecular mechanisms.
- Nuclear receptors (NRs) are transcriptional factors implicated in cancer development and progression.
- Estrogen-related receptor alpha (ERRα), an NR member, is linked to diverse cancer types.
Purpose of the Study:
- To review the multifaceted roles of Estrogen-related receptor alpha (ERRα) in various cancers.
- To highlight new developments and therapeutic implications concerning ERRα in oncology.
Main Methods:
- Review of existing literature on ERRα's function in cancer.
- Analysis of ERRα's regulatory targets, including genes involved in proliferation, angiogenesis, and metabolism.
- Examination of studies involving ERRα knockdown in cancer models.
Main Results:
- ERRα promotes cell proliferation and growth in endocrine-related cancers, independent of estrogen receptor alpha (ERα).
- ERRα knockdown significantly reduces tumor growth and malignancy in various cancer tissues and cell lines.
- ERRα regulates key factors like vascular endothelial growth factor (VEGF), cell cycle regulators, and metabolic genes.
Conclusions:
- ERRα plays a critical role in cancer initiation, progression, and malignancy through diverse molecular pathways.
- ERRα's influence extends to angiogenesis and cancer metabolism, offering a 'metabolic twist' to the disease.
- Targeting ERRα presents a potential therapeutic strategy for a wide range of cancers.
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