Oncogenic Role of Connective Tissue Growth Factor Is Associated with Canonical TGF-β Cascade in Colorectal Cancer

Genes (Basel). 2022 Apr 14;13(4):689. doi: 10.3390/genes13040689.


TGF-β signaling pathways promote tumour development and control several downstream genes such as CTGF and MMPs. This study aimed to investigate the association between CTGF and MMP-1 mRNA expressions with clinicopathological status and survival rate in colorectal cancer patients. We investigated expression levels of CTGF and MMP-1 genes in paraffin-embedded tumours and adjacent normal tissue blocks (ADJ) by Real Time-PCR. Then, the expression of Smad2 and Smad4 proteins in the TGF-β canonical pathway was evaluated by immunohistochemistry. Finally, the correlation between CTGF, MMP-1, and the canonical TGF-β-signalling pathway with the clinicopathological features was investigated. Expression levels of MMP-1and CTGF were higher in tumours compared with adjacent normal tissues. Overexpression levels of MMP-1 and CTGF were associated with lymph node metastasis, distant metastasis, tumour histopathological grading, advanced stage, and poor survival (p < 0.05). Additionally, a significant association between the upregulation of MMP-1 and tumour location was noted. Upregulation of Smad2 and Smad4 proteins were also significantly correlated with lymph node metastasis, distant metastasis, advanced stage, and poor survival (p < 0.0001). This study showed that canonical TGF-β signalling regulates both CTGF and MMP-1 expression and CRC progression. Moreover, TGF-β signalling and its downstream genes could be used as novel biomarkers and novel approaches for targeted therapy in CRC.

Keywords: CRC; CTGF; MMP-1; canonical TGF-β signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Connective Tissue Growth Factor* / genetics
  • Connective Tissue Growth Factor* / metabolism
  • Humans
  • Lymphatic Metastasis
  • Matrix Metalloproteinase 1 / genetics
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism


  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor
  • Matrix Metalloproteinase 1