title: Glutathione S-transferase mu2 suppresses cancer cell metastasis in non-small cell lung cancer.
abstract: Glutathione S-transferase mu2 (GST-M2) is a phase II detoxification enzyme. Low expression of GST-M2 in lung cancers is due to hypermethylation of its promoter. Lung cancer with the GST mu-null genotype is associated with shorter survival. However, a correlation between GST-M2 and important clinical parameters, as well as the migration of GST-M2-defective cells in lung cancer, has not been established. In the present study, we investigate the role of GST-M2 in cell migration and actin disassembly in lung cancer cells. GST-M2 and CCN2 mRNA levels were significantly reduced in non-small cell lung cancer (NSCLC) tumors when compared with matched normal lung tissues in 82 patients with NSCLC. We found that high expressions of both GST-M2 and CCN2 are correlated with favorable survival of patients with lung cancer when compared with similar patients without GST-M2 or CCN2 expression. GST-M2 can induce CCN2 expression by driving the CCN2 proximal promoter. Overexpression of GST-M2 decreases the formation of filopodia, resulting in remodeling of the reorganized cytoskeletons. Overexpression of GST-M2 significantly suppressed cancer cell migration on wound-healing assay. In addition, overexpression of GST-M2 dramatically reduced tumor growth and metastasis in a xenograft mouse model. These data highlight the potential of GST-M2 as a novel tumor suppressor. GST-M2 increases the expression of CCN2 in lung cancer cells, which inhibits cancer cell migration in lung cancer and animal models.
authors: Institute of Medicine, Chung Shan Medical University, Taichung City 40203,Taiwan.
authors: Sheau-Chung
authors: SC
authors: Tang
authors: Chih-Hsien
authors: CH
authors: Wu
authors: Chien-Hung
authors: CH
authors: Lai
authors: Wen-Wei
authors: WW
authors: Sung
authors: Wan-Jung
authors: WJ
authors: Yang
authors: Lee-Chun
authors: LC
authors: Tang
authors: Chung-Ping
authors: CP
authors: Hsu
authors: Jiunn-Liang
authors: JL
authors: Ko
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005260:Female; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: C526317:CCN2 protein, human; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; D005982:Glutathione Transferase; C412602:glutathione S-transferase Mu 2