Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinoma (2024)

Lai, W. T., Li, Y. J., Wu, S. B., Yang, C. N., Wu, T. S., Wei, Y. H., & Deng, Y. T. (2018). 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, 117(3), 212-219. https://doi.org/10.1016/j.jfma.2017.04.003

Lai, Wei Ting ; Li, Yue Ju ; Wu, Shi Bei et al. / Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinoma. In: Journal of the Formosan Medical Association. 2018 ; Vol. 117, No. 3. pp. 212-219.

@article{c023f7537b6f4478a3b516e908998c31,

title = "Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinoma",

abstract = "Background/Purpose: 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.",

keywords = "CTGF, Metabolism, Mitochondrion, OSCC, mtTFA",

author = "Lai, {Wei Ting} and Li, {Yue Ju} and Wu, {Shi Bei} and Yang, {Cheng Ning} and Wu, {Tai Sheng} and Wei, {Yau Huei} and Deng, {Yi Ting}",

note = "Publisher Copyright: {\textcopyright} 2017",

year = "2018",

month = mar,

doi = "10.1016/j.jfma.2017.04.003",

language = "英语",

volume = "117",

pages = "212--219",

journal = "Journal of the Formosan Medical Association",

issn = "0929-6646",

number = "3",

}

Lai, WT, Li, YJ, Wu, SB, Yang, CN, Wu, TS, Wei, YH & Deng, YT 2018, '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, vol. 117, no. 3, pp. 212-219. https://doi.org/10.1016/j.jfma.2017.04.003

Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinoma. / Lai, Wei Ting; Li, Yue Ju; Wu, Shi Bei et al.
In: Journal of the Formosan Medical Association, Vol. 117, No. 3, 03.2018, p. 212-219.

Research output: Contribution to journal › Journal Article › peer-review

TY - JOUR

T1 - Connective tissue growth factor decreases mitochondrial metabolism through ubiquitin-mediated degradation of mitochondrial transcription factor A in oral squamous cell carcinoma

AU - Lai, Wei Ting

AU - Li, Yue Ju

AU - Wu, Shi Bei

AU - Yang, Cheng Ning

AU - Wu, Tai Sheng

AU - Wei, Yau Huei

AU - Deng, Yi Ting

N1 - Publisher Copyright:© 2017

PY - 2018/3

Y1 - 2018/3

N2 - Background/Purpose: 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.

AB - Background/Purpose: 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.

KW - CTGF

KW - Metabolism

KW - Mitochondrion

KW - OSCC

KW - mtTFA

UR - http://www.scopus.com/inward/record.url?scp=85018732180&partnerID=8YFLogxK

U2 - 10.1016/j.jfma.2017.04.003

DO - 10.1016/j.jfma.2017.04.003

M3 - 文章

C2 - 28438434

AN - SCOPUS:85018732180

SN - 0929-6646

VL - 117

SP - 212

EP - 219

JO - Journal of the Formosan Medical Association

JF - Journal of the Formosan Medical Association

IS - 3

ER -

Lai WT, Li YJ, Wu SB, Yang CN, Wu TS, Wei YH et al. 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. 2018 Mar;117(3):212-219. doi: 10.1016/j.jfma.2017.04.003