title: Manganese superoxide dismutase induces migration and invasion of tongue squamous cell carcinoma via H2O2-dependent Snail signaling.
abstract: Our previous studies had revealed that the dysregulation of manganese superoxide dismutase (SOD2) expression was a frequent event in tongue squamous cell carcinoma (TSCC) and may be associated with enhanced metastatic potential. To further evaluate the mechanism of SOD2-mediated metastasis in TSCC, TSCC cell lines with different metastatic potentials (i.e., the highly metastatic UM1 line and the UM2 line, which displays fewer metastases) were used. Compared to UM2 cells, UM1 cells exhibited significantly higher SOD2 activity and intracellular H(2)O(2); higher protein levels of Snail, MMP1, and pERK1/2; lower protein levels of E-cadherin; and no difference in catalase activity. Upon knockdown of SOD2 by RNA interference, UM1 cells displayed significantly reduced migration and invasion abilities; reduced activities of SOD2; lower intracellular H(2)O(2); decreased protein levels of Snail, MMP1, and pERK1/2; and increased protein levels of E-cadherin. The migration and invasion abilities of UM2 and SOD2 shRNA-transfected UM1 cells were enhanced by H(2)O(2) treatment and accompanied by increased protein levels of Snail, MMP1, and pERK1/2 and decreased protein levels of E-cadherin. Moreover the migration and invasion abilities of UM1 cells were decreased after catalase treatment. Thus, we conclude that the SOD2-dependent production of H(2)O(2) contributes to both the migration and the invasion of TSCC via the Snail signaling pathway, through increased Snail, MMP1, and pERK1/2 protein levels and the repression of the E-cadherin protein.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Liu
authors.forename: Su
authors.initials: S
authors.lastname: Li
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Cai
authors.forename: Anxun
authors.initials: A
authors.lastname: Wang
authors.forename: Qianting
authors.initials: Q
authors.lastname: He
authors.forename: Chaoxu
authors.initials: C
authors.lastname: Zheng
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.forename: Xueqiang
authors.initials: X
authors.lastname: Ding
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology*; D002374:Catalase / Q000378:metabolism; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010084:Oxidation-Reduction; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014062:Tongue Neoplasms / Q000201:enzymology / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism*; D014945:Wound Healing; D000099156:Superoxide Dismutase 2
chemical_list: D002374:Catalase; D006861:Hydrogen Peroxide; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D013482:Superoxide Dismutase; D014157:Transcription Factors; D000099156:Superoxide Dismutase 2