Role of Bmi-1 in regulation of ionizing irradiation-induced epithelial-mesenchymal transition and migration of breast cancer cells

• Published in: PloS one Vol. 10; no. 3; p. e0118799
• Main Authors: Yuan, Weiwei, Yuan, Ye, Zhang, Tao, Wu, Shiyong
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.03.2015; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Analysis; Apoptosis; Bmi protein; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cancer cells; Care and treatment; Cell Line, Tumor; Cell migration; Cell Movement - radiation effects; Epithelial-Mesenchymal Transition - radiation effects; Female; Gene expression; Humans; I.R. radiation; Inhibition; Ionizing radiation; Irradiation; MCF-7 Cells; Mesenchyme; Metastases; Oxidative stress; Phosphatidylinositol 3-Kinases - metabolism; Phosphoinositide-3 Kinase Inhibitors; Polycomb group proteins; Polycomb Repressive Complex 1 - antagonists & inhibitors; Polycomb Repressive Complex 1 - genetics; Polycomb Repressive Complex 1 - metabolism; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Radiation; Radiation therapy; Radiation, Ionizing; RNA Interference; RNA, Small Interfering - metabolism; Signal Transduction; Signaling; Stem cells; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0118799

Radiotherapy is a widely used treatment for cancer. However, recent studies suggest that ionizing radiation (IR) can promote tumor invasion and metastasis. Bmi-1, a member of the polycomb group protein family, has been observed as a regulator of oxidative stress and promotes metastasis in some tumors. But, its potential role in the metastasis induced by IR of breast cancer has not been explored. In our study, we found that increased levels of Bmi-1 were correlated to EMT of breast cancer cells. Through analyzing the EMT state and metastasis of breast cancer induced by IR, we found the metastatic potential of breast cancer cells can either be inhibited or accelerated by IR following a time-dependent pattern. Silencing Bmi-1 completely abolished the ability of the IR to alter, reduce or increase, the migration of breast cancer cells. Also, when Bmi-1 was knocked down, the effect of inhibition of PI3K/AKT signaling on EMT affected by IR was blocked. These results suggest that Bmi-1 is a key gene in regulation of EMT and migration of breast cancer cells induced by IR through activation of PI3K/AKT signaling; therefore, Bmi-1 could be a new target for inhibiting metastasis caused by IR.