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

Journal article


Hosseini, Shaghayegh, Rejali, L., Pezeshkian, Z., Malekian, Mahtash, Fatemi, Nayeralsadat, Peyravian, N., Hadizadeh, M., Mohsenifar, Zhaleh, Khanabadi, Binazir, Farzam, Maral, Sherkat, Ghazal, Asadzadeh Aghdaei, H., Nazemalhosseini Mojarad, Ehsan and Bonab, M. 2022. Oncogenic role of connective tissue growth factor is associated with canonical TGF-β cascade in colorectal cancer. Genes. 13 (4), p. e689. https://doi.org/10.3390/genes13040689
AuthorsHosseini, Shaghayegh, Rejali, L., Pezeshkian, Z., Malekian, Mahtash, Fatemi, Nayeralsadat, Peyravian, N., Hadizadeh, M., Mohsenifar, Zhaleh, Khanabadi, Binazir, Farzam, Maral, Sherkat, Ghazal, Asadzadeh Aghdaei, H., Nazemalhosseini Mojarad, Ehsan and Bonab, M.
AbstractTGF-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.
KeywordsMMP-1; CTGF; Canonical TGF-β signalling; CRC
Year2022
JournalGenes
Journal citation13 (4), p. e689
PublisherMDPI
ISSN2073-4425
Digital Object Identifier (DOI)https://doi.org/10.3390/genes13040689
Official URLhttps://www.mdpi.com/2073-4425/13/4/689
FunderShahid Beheshti University of Medical Sciences
Publication dates
Online14 Apr 2022
Publication process dates
Accepted05 Apr 2022
Deposited19 May 2023
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https://repository.canterbury.ac.uk/item/9401x/oncogenic-role-of-connective-tissue-growth-factor-is-associated-with-canonical-tgf-cascade-in-colorectal-cancer

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