| Mitochondrial dysfunction promotes cell migration via reactive oxygen species-enhanced β5-integrin expression in human gastric cancer SC-M1 cells. | |
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MedLine Citation:
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PMID: 22561002 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: Mitochondrial dysfunction has been shown to promote cancer cell migration. However, molecular mechanism by which mitochondrial dysfunction enhances gastric cancer (GC) cell migration remains unclear. METHODS: Mitochondria specific inhibitors, oligomycin and antimycin A, were used to induce mitochondrial dysfunction and to enhance cell migration of human gastric cancer SC-M1 cells. Antioxidant N-acetylcysteine (NAC) was used for evaluating the effect of reactive oxygen species (ROS). Protein expressions of epithelial-to-mesenchymal transition (EMT) markers and the cell-extracellular matrix (ECM) adhesion molecules, the integrin family, were analyzed. A migratory subpopulation of SC-M1 cells (SC-M1-3rd) was selected using a transwell assay for examining the association of mitochondrial bioenergetic function, intracellular ROS content and β5-integrin expression. Clinicopathologic characteristics of β5-integrin expression were analyzed in GC specimens by immunohistochemical staining. RESULTS: Treatments with mitochondrial inhibitors elevated mitochondria-generated ROS and cell migration of SC-M1 cells. The protein expression of β5-integrin and cell surface expression of αvβ5-integrin were upregulated, and which were suppressed by NAC. Pretreatments with NAC and anti-αvβ5-integrin neutralizing antibody respectively prevented the mitochondrial dysfunction-induced cell migration. The selected migratory SC-M1-3rd cells showed impaired mitochondrial function, higher mitochondria-generated ROS, and increased β5-integrin expression. The migration ability was also repressed by anti-αvβ5-integrin neutralizing antibody. In clinical specimens, GCs with higher β5-integrin protein expression had more aggressive behavior. CONCLUSIONS: Mitochondrial dysfunction may lead to GC progression by enhancing migration through mitochondria-generated ROS mediated β5-integrin expression. GENERAL SIGNIFICANCE: These results support the role of mitochondrial dysfunction in GC progression. |
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Authors:
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Wen-Yi Hung; Kuo-Hung Huang; Chew-Wun Wu; Chin-Wen Chi; Hwa-Li Kao; Anna Fen-Yau Li; Pen-Hui Yin; Hsin-Chen Lee |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-26 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: - ISSN: 0006-3002 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-5-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier B.V. All rights reserved. |
Affiliation:
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Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taiwan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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