Abstract 1135: C-myc-SOD2/Bmi1 pathway mediates cancer stem-like cell migration and invasion in tongue squamous cell carcinoma
Authors: Qianting He, Zhonghua Liu, Leitao Zhang, Tingting Zhao, Luodan Zhao, Dan Chen, Yu Chen, Xueqiang Ding, Xiaofeng Zhou, Anxun Wang
Journal: Cancer Research (2014)

Abstract Our previous studies had revealed that over-expression of manganese superoxide dismutase (SOD2) is a frequent event in tongue squamous cell carcinoma (TSCC) [BMC Cancer. 2010 10:365], and it contributes to the enhanced metastatic potential of TSCC through regulating cell migration and invasion [Free Radic Biol Med. 2012 53(1):44-50]. In the current study, our immunohistochemistry analysis confirmed the over-expression of SOD2 in TSCC patient cohort, and further revealed that over-expression of Bmi1, a member of the Polycomb group of chromatin-modifier proteins that is essential for stem cell self-renewal, is also a common event in premalignant dysplasia, primary SCC, and lymph node metastases. Furthermore, the over-expression of BMI1 is associated with poor prognosis. More importantly, a statistically significant correlation was observed between Bmi1 expression and SOD2 expression. These observations were supported by our in vitro studies, in which knockdown of SOD2/Bmi1 in TSCC cell line (UM1) or stem cell marker-expressing side population (SP) of the UM1 cells led to reduced cell migration and invasion, as well as decreases in the SP proportion (in UM1 cells), proliferation, sphere and clone formation and reduced expression of stem cell markers (ABCG, Nanog, Bmi1). Interesting, knockdown of SOD2 in UM1 or SP led to reduced expression of Bmi1, and knockdown of Bmi1 led to reduced expression of SOD2, which mirrors the observed correlation between Bmi1 and SOD2 in the TSCC patient cohort. Since c-myc is a known oncogene that has been showed to regulate both Bmi1 and SOD2, we further examined the role of c-myc-SOD2/Bmi1 pathway in TSCC. Direct binding of c-myc protein to the E-box in the Bmi1/SOD2 promoter were demonstrated by ChIP assay and Luciferase assay. Moreover, knockdown of c-myc in UM1 or SP cells led to reduced expression of both Bmi1 and SOD2, as well as reduced cell migration, and invasion, reduced expression of stem cell markers, decreases in the SP proportion (in UM1 cells), inhibition in cell proliferation, sphere and clone formation. Taken together, these data suggest that Bmi1 and SOD2 are two major factors in the initiation and progression of TSCC, and play an important role in the migration and invasion of TSCC cells. C-myc directly regulated the expression of Bmi1 and SOD2, and thus mediated the migration and invasion and maintaining the stemmness of the CSC in TSCC. Citation Format: Qianting He, Zhonghua Liu, Leitao Zhang, Tingting Zhao, Luodan Zhao, Dan Chen, Yu Chen, Xueqiang Ding, Xiaofeng Zhou, Anxun Wang. C-myc-SOD2/Bmi1 pathway mediates cancer stem-like cell migration and invasion in tongue squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1135. doi:10.1158/1538-7445.AM2014-1135