摘要
Breast cancer,one of the most frequent cancer types,is a leading cause of death in women worldwide.Estrogen receptor(ER)αis 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.
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。
基金
Project supported by the National Cancer Institute(No.R01CA197865),the Ride Cincinnati Award
the National Center for Advancing Translation Science of the National Institutes of Health(No.UL1TR001425),USA
