ERα inhibits epithelial-mesenchymal transition by suppressing Bmi1 in breast cancer.

Abstract

In human breast cancer, estrogen receptor-α (ERα) suppresses epithelial-mesenchymal transition (EMT) and stemness, two crucial parameters for tumor metastasis; however, the underlying mechanism by which ERα regulates these two processes remains largely unknown. Bmi1, the polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog, regulates EMT transition, maintains the self-renewal capacity of stem cells, and is frequently overexpressed in human cancers. In the present study, ERα upregulated the expression of the epithelial marker, E-cadherin, in breast cancer cells through the transcriptional down-regulation of Bmi1. Furthermore, ERα overexpression suppressed the migration, invasion, and EMT of breast cancer cells. Notably, overexpression of ERα significantly decreased the CD44high/CD24low cell population and inhibited the capacity for mammosphere formation in ERα-negative breast cancer cells. In addition, overexpression of Bmi1 attenuated the ERα-mediated suppression of EMT and cell stemness. Immunohistochemistry revealed an inverse association of ERα and Bmi1 expression in human breast cancer tissue. Taken together, our findings suggest that ERα inhibits EMT and stemness through the downregulation of Bmi1.

• Authors: Xiao-Long Wei, Xiao-Wei Dou, Jing-Wen Bai, Xiang-Rong Luo, Si-Qi Qiu, Di-Di Xi, Wen-He Huang, Cai-Wen Du, Kwan Man, Guo-Jun Zhang
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 25 Pg. 21704-17 (Aug 28 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26023734 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BMI1 protein, human
• CD24 Antigen
• CD44 protein, human
• Cadherins
• ESR1 protein, human
• Estrogen Receptor alpha
• Estrogens
• Hyaluronan Receptors
• Polycomb Repressive Complex 1

Topics

• Animals
• Breast Neoplasms (metabolism)
• CD24 Antigen (metabolism)
• Cadherins (metabolism)
• Cell Movement
• Epithelial-Mesenchymal Transition
• Estrogen Receptor alpha (metabolism)
• Estrogens (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Hyaluronan Receptors (metabolism)
• Immunohistochemistry
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Polycomb Repressive Complex 1 (antagonists & inhibitors, metabolism)
• Promoter Regions, Genetic
• Protein Binding
• Signal Transduction
• Stem Cells (cytology)
• Wound Healing