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

Shaghayegh Hosseini; Leili Rejali; Zahra Pezeshkian; Mahtash Malekian; Nayeralsadat Fatemi; Noshad Peyravian; Mahrooyeh Hadizadeh; Zhaleh Mohsenifar; Binazir Khanabadi; Maral Farzam; Ghazal Sherkat; Hamid Asadzadeh Aghdaei; Ehsan Nazemalhosseini Mojarad; Maziar Ashrafian Bonab

doi:10.3390/genes13040689

Genes (Apr 2022)

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

Shaghayegh Hosseini,
Leili Rejali,
Zahra Pezeshkian,
Mahtash Malekian,
Nayeralsadat Fatemi,
Noshad Peyravian,
Mahrooyeh Hadizadeh,
Zhaleh Mohsenifar,
Binazir Khanabadi,
Maral Farzam,
Ghazal Sherkat,
Hamid Asadzadeh Aghdaei,
Ehsan Nazemalhosseini Mojarad,
Maziar Ashrafian Bonab

Affiliations

Shaghayegh Hosseini: 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
Leili Rejali: 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
Zahra Pezeshkian: 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
Mahtash Malekian: 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
Nayeralsadat Fatemi: 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
Noshad Peyravian: 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
Mahrooyeh Hadizadeh: Faculty of Health and Wellbeing, Canterbury Christ Church University, Canterbury CT1 1QU, UK
Zhaleh Mohsenifar: Department of Pathology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran 19839-63113, Iran
Binazir Khanabadi: 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
Maral Farzam: Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 19857-17411, Iran
Ghazal Sherkat: Medicin Faculty of Mashhad Branch, Islamic Azad University, Mashhad 91871-47578, Iran
Hamid Asadzadeh Aghdaei: 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
Ehsan Nazemalhosseini Mojarad: Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 19857-17411, Iran
Maziar Ashrafian Bonab: Kent and Medway Medical School, Canterbury CT2 7FS, UK

DOI: https://doi.org/10.3390/genes13040689
Journal volume & issue: Vol. 13, no. 4
p. 689

Abstract

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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 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.

Published in Genes

ISSN: 2073-4425 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General): Genetics
Website: http://www.mdpi.com/journal/genes/

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