Oncogenic role of connective tissue growth factor is associated with canonical TGF-β cascade in colorectal cancer

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

doi:10.3390/genes13040689

Oncogenic role of connective tissue growth factor is associated with canonical TGF-β cascade in colorectal cancer

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

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

6 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	e689
Journal	Genes
Volume	13
Issue number	4
DOIs	https://doi.org/10.3390/genes13040689
Publication status	Published - 14 Apr 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

CRC
CTGF
Canonical TGF-β signalling
MMP-1

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Rejali, L., Pezeshkian, Z., Peyravian, N., Hadizadeh, M., Aghdaei, H. A., Bonab, M., Hosseini, S., Malekian, M., Fatemi, N., Mohsenifar, Z., Khanabadi, B., Farzam, M., Sherkat, G., & Nazemalhosseini Mojarad, E. (2022). Oncogenic role of connective tissue growth factor is associated with canonical TGF-β cascade in colorectal cancer. Genes, 13(4), e689. https://doi.org/10.3390/genes13040689

@article{35cabc2fe77a4cae816c964e822e39e0,

title = "Oncogenic role of connective tissue growth factor is associated with canonical TGF-β cascade in colorectal cancer",

abstract = "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, Canonical TGF-β signalling, MMP-1",

author = "Leili Rejali and Zahra Pezeshkian and Noshad Peyravian and Mahrooyeh Hadizadeh and Aghdaei, \{Hamid Asadzadeh\} and Maziar Bonab and Shaghayegh Hosseini and Mahtash Malekian and Nayeralsadat Fatemi and Zhaleh Mohsenifar and Binazir Khanabadi and Maral Farzam and Ghazal Sherkat and \{Nazemalhosseini Mojarad\}, Ehsan",

year = "2022",

month = apr,

day = "14",

doi = "10.3390/genes13040689",

language = "English",

volume = "13",

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journal = "Genes",

issn = "2073-4425",

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Rejali, L, Pezeshkian, Z, Peyravian, N, Hadizadeh, M, Aghdaei, HA, Bonab, M, Hosseini, S, Malekian, M, Fatemi, N, Mohsenifar, Z, Khanabadi, B, Farzam, M, Sherkat, G & Nazemalhosseini Mojarad, E 2022, 'Oncogenic role of connective tissue growth factor is associated with canonical TGF-β cascade in colorectal cancer', Genes, vol. 13, no. 4, pp. e689. https://doi.org/10.3390/genes13040689

TY - JOUR

T1 - Oncogenic role of connective tissue growth factor is associated with canonical TGF-β cascade in colorectal cancer

AU - Rejali, Leili

AU - Pezeshkian, Zahra

AU - Peyravian, Noshad

AU - Hadizadeh, Mahrooyeh

AU - Aghdaei, Hamid Asadzadeh

AU - Bonab, Maziar

AU - Hosseini, Shaghayegh

AU - Malekian, Mahtash

AU - Fatemi, Nayeralsadat

AU - Mohsenifar, Zhaleh

AU - Khanabadi, Binazir

AU - Farzam, Maral

AU - Sherkat, Ghazal

AU - Nazemalhosseini Mojarad, Ehsan

PY - 2022/4/14

Y1 - 2022/4/14

N2 - 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.

AB - 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.

KW - CRC

KW - CTGF

KW - Canonical TGF-β signalling

KW - MMP-1

U2 - 10.3390/genes13040689

DO - 10.3390/genes13040689

M3 - Article

SN - 2073-4425

VL - 13

SP - e689

JO - Genes

JF - Genes

IS - 4

ER -

Oncogenic role of connective tissue growth factor is associated with canonical TGF-β cascade in colorectal cancer

Abstract

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Keywords

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