Abstract
Breast cancer, one of the most frequent cancer types, is a leading cause of death in women worldwide. Estrogen receptor (ER) a is a nuclear hormone receptor that plays key roles in mammary gland development and breast cancer. About 75% of breast cancer cases are diagnosed as ER-positive; however, nearly half of these cancers are either intrinsically or inherently resistant to the current anti-estrogen therapies. Recent studies have identified an ER coactivator, Mediator Subunit 1 (MED1), as a unique, tissue-specific cofactor that mediates breast cancer metastasis and treatment resistance. MED1 is overexpressed in over 50% of human breast cancer cases and co-amplifies with another important breast cancer gene, receptor tyrosine kinase HER2. Clinically, MED1 expression highly correlates with poor disease-free survival of breast cancer patients, and recent studies have reported an increased frequency of MED1 mutations in the circulating tumor cells of patients after treatment. In this review, we discuss the biochemical characterization of MED1 and its associated MED1/Mediator complex, its crosstalk with HER2 in anti-estrogen resistance, breast cancer stem cell formation, and metastasis both in vitro and in vivo. Furthermore, we elaborate on the current advancements in targeting MED1 using state-of-the-art RNA nanotechnology and discuss the future perspectives as well.
概 要
在这篇综述中, 我们讨论了雌激素受体共激活子转录中介体亚基 1 (MED1) 作为独特的组织特异性辅因子在乳腺癌干细胞形成、 转移和治疗抗性中的关键作用。 此外, 我们详细介绍了目前使用最先进的 RNA 纳米技术靶标 MED1 的成果, 并提出了未来的展望。
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Acknowledgments
We would like to thank Mr. Glenn DOERMAN (University of Cincinnati, Cincinnati, OH, USA) for figure illustrations in this review.
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Project supported by the National Cancer Institute (No. R01CA 197865), the Ride Cincinnati Award, and the National Center for Advancing Translation Science of the National Institutes of Health (No. UL1TR001425), USA
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Leonard, M., Zhang, X. Estrogen receptor coactivator Mediator Subunit 1 (MED1) as a tissue-specific therapeutic target in breast cancer. J. Zhejiang Univ. Sci. B 20, 381–390 (2019). https://doi.org/10.1631/jzus.B1900163
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DOI: https://doi.org/10.1631/jzus.B1900163
Key words
- Mediator Subunit 1 (MED1)
- Mediator
- Estrogen receptor
- Breast cancer
- Endocrine resistance
- RNA nanotechnology