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

Genes

Hamid Asadzadeh Aghdaei¹  Binazir Khanabadi¹  Zahra Pezeshkian¹  Noshad Peyravian¹  Mahtash Malekian¹  Nayeralsadat Fatemi¹  Shaghayegh Hosseini¹  Leili Rejali¹  Zhaleh Mohsenifar²  Mahrooyeh Hadizadeh³  Maral Farzam⁴  Ehsan Nazemalhosseini Mojarad⁴  Maziar Ashrafian Bonab⁵  Ghazal Sherkat⁶ 

[1] Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 19857-17411, Iran;Department of Pathology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran;Faculty of Health and Wellbeing, Canterbury Christ Church University, Canterbury CT1 1QU, UK;Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 19857-17411, Iran;Kent and Medway Medical School, Canterbury CT2 7FS, UK;Medicin Faculty of Mashhad Branch, Islamic Azad University, Mashhad 91871-47578, Iran;

关键词: MMP-1;    CTGF;    canonical TGF-β signalling;    CRC;   

DOI  :  10.3390/genes13040689

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown