Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinoma
Deregulation of metabolic pathways is one of the hallmarks of cancer progression. Connective tissue growth factor (CTGF/CCN2) acts as a tumor suppressor in oral squamous cell carcinoma (OSCC). However, the role of CTGF in modulating cancer metabolism is still unclear. Methods: OSCC cells stably over...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-03-01
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| Series: | Journal of the Formosan Medical Association |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0929664617302450 |
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| author | Wei-Ting Lai Yue-Ju Li Shi-Bei Wu Cheng-Ning Yang Tai-Sheng Wu Yau-Huei Wei Yi-Ting Deng |
| author_facet | Wei-Ting Lai Yue-Ju Li Shi-Bei Wu Cheng-Ning Yang Tai-Sheng Wu Yau-Huei Wei Yi-Ting Deng |
| author_sort | Wei-Ting Lai |
| collection | DOAJ |
| description | Deregulation of metabolic pathways is one of the hallmarks of cancer progression. Connective tissue growth factor (CTGF/CCN2) acts as a tumor suppressor in oral squamous cell carcinoma (OSCC). However, the role of CTGF in modulating cancer metabolism is still unclear.
Methods: OSCC cells stably overexpressing CTGF (SAS/CTGF) and shRNA against CTGF (TW2.6/shCTGF) were established. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were examined by the Seahorse XF24 analyzer. The expression of CTGF and mitochondrial biogenesis related genes was measured by real-time polymerase chain reaction or Western blot analysis.
Results: CTGF decreased OCR, ECAR, adenosine triphosphate (ATP) generation, mitochondrial DNA (mtDNA), and mitochondrial transcription factor A (mtTFA) protein expression in OSCC cells. Overexpression of mtTFA restored CTGF-decreased OCR, ECAR, mtDNA copy number, migration and invasion of SAS/CTGF cells. Immunoprecipitation assay showed a higher level of ubiquitinated mtTFA protein after CTGF treatment. MG132, an inhibitor of proteasomal degradation, reversed the effect of CTGF on mtTFA protein expression in SAS cells.
Conclusion: CTGF can decrease glycolysis, mitochondrial oxidative phosphorylation, ATP generation, and mtDNA copy number by increasing mtTFA protein degradation through ubiquitin proteasome pathway and in turn reduces migration and invasion of OSCC cells. Therefore, CTGF may be developed as a potential additive therapeutic drug for oral cancer in the near future. |
| first_indexed | 2024-04-13T14:53:32Z |
| format | Article |
| id | doaj.art-83df710c03c847d286cddd90fcacdbac |
| institution | Directory Open Access Journal |
| issn | 0929-6646 |
| language | English |
| last_indexed | 2024-04-13T14:53:32Z |
| publishDate | 2018-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of the Formosan Medical Association |
| spelling | doaj.art-83df710c03c847d286cddd90fcacdbac2022-12-22T02:42:31ZengElsevierJournal of the Formosan Medical Association0929-66462018-03-01117321221910.1016/j.jfma.2017.04.003Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinomaWei-Ting Lai0Yue-Ju Li1Shi-Bei Wu2Cheng-Ning Yang3Tai-Sheng Wu4Yau-Huei Wei5Yi-Ting Deng6Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, TaiwanGraduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, TaiwanInstitute of Biotechnology in Medicine, National Yang-Ming University, Taipei, TaiwanGraduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, TaiwanGraduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, TaiwanInstitute of Biotechnology in Medicine, National Yang-Ming University, Taipei, TaiwanGraduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, TaiwanDeregulation of metabolic pathways is one of the hallmarks of cancer progression. Connective tissue growth factor (CTGF/CCN2) acts as a tumor suppressor in oral squamous cell carcinoma (OSCC). However, the role of CTGF in modulating cancer metabolism is still unclear. Methods: OSCC cells stably overexpressing CTGF (SAS/CTGF) and shRNA against CTGF (TW2.6/shCTGF) were established. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were examined by the Seahorse XF24 analyzer. The expression of CTGF and mitochondrial biogenesis related genes was measured by real-time polymerase chain reaction or Western blot analysis. Results: CTGF decreased OCR, ECAR, adenosine triphosphate (ATP) generation, mitochondrial DNA (mtDNA), and mitochondrial transcription factor A (mtTFA) protein expression in OSCC cells. Overexpression of mtTFA restored CTGF-decreased OCR, ECAR, mtDNA copy number, migration and invasion of SAS/CTGF cells. Immunoprecipitation assay showed a higher level of ubiquitinated mtTFA protein after CTGF treatment. MG132, an inhibitor of proteasomal degradation, reversed the effect of CTGF on mtTFA protein expression in SAS cells. Conclusion: CTGF can decrease glycolysis, mitochondrial oxidative phosphorylation, ATP generation, and mtDNA copy number by increasing mtTFA protein degradation through ubiquitin proteasome pathway and in turn reduces migration and invasion of OSCC cells. Therefore, CTGF may be developed as a potential additive therapeutic drug for oral cancer in the near future.http://www.sciencedirect.com/science/article/pii/S0929664617302450CTGFMetabolismMitochondrionmtTFAOSCC |
| spellingShingle | Wei-Ting Lai Yue-Ju Li Shi-Bei Wu Cheng-Ning Yang Tai-Sheng Wu Yau-Huei Wei Yi-Ting Deng Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinoma Journal of the Formosan Medical Association CTGF Metabolism Mitochondrion mtTFA OSCC |
| title | Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinoma |
| title_full | Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinoma |
| title_fullStr | Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinoma |
| title_full_unstemmed | Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinoma |
| title_short | Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinoma |
| title_sort | connective tissue growth factor decreases mitochondrial metabolism through ubiquitin mediated degradation of mitochondrial transcription factor a in oral squamous cell carcinoma |
| topic | CTGF Metabolism Mitochondrion mtTFA OSCC |
| url | http://www.sciencedirect.com/science/article/pii/S0929664617302450 |
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