Effects of Connective Tissue Growth Factor on Cancer Metabolism
Date Issued
2012
Date
2012
Author(s)
Lai, Wei-Ting
Abstract
Purpose:
Connective tissue growth factor (CTGF) has been shown to inhibit the metastatic activity of oral squamous cell carcinoma (OSCC) and non-small-cell lung carcinoma (NSCLC). We hypotheses that CTGF could interfere cancer metabolism and regulate tumor progression.
Method:
Metabolism pathways, including glycolysis and oxygen phosphorylation were measured by XF24 bioenergetic assay in normal epithelial, OSCC and NSCLC cells. Migration and invasion abilities of cells were performed by modified Boyden chamber assay.
Result:
We observed that CTGF reduced cellular ATP production and lactate levels (P <0.01, P <0.05), which may be caused by decreased glycolysis and oxygen phosphorylation in OSCC and NSCLC (P <0.05, P <0.01), but no significant effect on normal epithelial cells. This small secreted protein also inhibited oxidative phosphorylation compensation (P <0.05), and reduced mitochondrial activity. Our data demonstrated that CTGF decreased mitochondrial DNA copy numbers, which resulted in the repression of cancer cell migration and invasion abilities (P <0.01). We observed that mitochondrial transcription factor A (mtTFA; TFAM) protein expression negatively correlated with CTGF. mtTFA expression was positively associated with poor survival in OSCC patients (P <0.01). Interestingly, transiently knockdown endogenous mtTFA decreased OSCC and NSCLC migration and invasion abilities (P <0.01). mtTFA overexpression restored CTGF-inhibited OSCC and NSCLC progression in vitro and in vivo (P <0.05, P <0.01).
Conclusion:
CTGF, a key regulator of cancer metabolism, decreased cancer metabolism, including glycolysis and oxygen phosphorylation via inhibiting mtTFA expression, and resulted in a reduction in cancer progression in OSCC and NSCLC cells.
Subjects
OSCC
NSCLC
cancer progression
CTGF
mtTFA
metabolism
SDGs
Type
thesis
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