Role of Bmi-1 in regulation of ionizing irradiation-induced epithelial-mesenchymal transition and migration of breast cancer cells.
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.
Department of Oncology, the General Hospital of Chengdu Military District, Chengdu, Sichuan, P. R. China; Department of Chemistry and Biochemistry, and Edison Biotechnology Institute, Ohio University, Athens, Ohio, 45701, United States of America.
Weiwei
W
Yuan
Department of Chemistry and Biochemistry, and Edison Biotechnology Institute, Ohio University, Athens, Ohio, 45701, United States of America.
Ye
Y
Yuan
Department of Oncology, the General Hospital of Chengdu Military District, Chengdu, Sichuan, P. R. China.
Tao
T
Zhang
Department of Chemistry and Biochemistry, and Edison Biotechnology Institute, Ohio University, Athens, Ohio, 45701, United States of America.
Shiyong
S
Wu
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects; D058750:Epithelial-Mesenchymal Transition / Q000528:radiation effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D063150:Polycomb Repressive Complex 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011839:Radiation, Ionizing; D015398:Signal Transduction
D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D063150:Polycomb Repressive Complex 1; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; C069077:BMI1 protein, human