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Review
. 2022 Sep 7;28(33):4744-4761.
doi: 10.3748/wjg.v28.i33.4744.

Regulation of transforming growth factor-β signaling as a therapeutic approach to treating colorectal cancer

Jana Maslankova  1 , Ivana Vecurkovska  1 , Miroslava Rabajdova  1 , Jana Katuchova  2 , Milos Kicka  3 , Michala Gayova  4 , Vladimir Katuch  5
Affiliations
Review

Regulation of transforming growth factor-β signaling as a therapeutic approach to treating colorectal cancer

Jana Maslankova et al. World J Gastroenterol. .

Abstract

According to data from 2020, Slovakia has long been among the top five countries with the highest incidence rate of colorectal cancer (CRC) worldwide, and the rate is continuing to rise every year. In approximately 80% of CRC cases, allelic loss (loss of heterozygosity, LOH) occurs in the long arm of chromosome 18q. The most important genes that can be silenced by 18q LOH or mutations are small mothers against decapentaplegic homolog (SMAD) 2 and SMAD4, which are intracellular mediators of transforming growth factor (TGF)-β superfamily signals. TGF-β plays an important role in the pro-oncogenic processes, including such properties as invasion, epithelial-mesenchymal transition (commonly known as EMT), promotion of angiogenesis, and immunomodulatory effects. Several recent studies have reported that activation of TGF-β signaling is related to drug resistance in CRC. Because the mechanisms of drug resistance are different between patients in different stages of CRC, personalized treatment is more effective. Therefore, knowledge of the activation and inhibition of factors that affect the TGF-β signaling pathway is very important.

Keywords: Colorectal cancer; Marker; Signaling pathway; Small mothers against decapentaplegic homologs; Transforming growth factor-beta.

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Conflict of interest statement

Conflict-of-interest statement: The authors declare having no conflict of interests for this article.

Figures

Figure 1
Figure 1
Representation of individual colorectal cancer subtypes.
Figure 2
Figure 2
Three genetic and epigenetic aberrations of colorectal cancer formation. LOH: Loss of heterozygosity; TGF: Transforming growth factor.
Figure 3
Figure 3
Transforming growth factor-beta superfamily signal transduction. TGF: Transforming growth factor; EMT: Epithelial-mesenchymal transition; ERK: Extracellular signal-regulated kinase; BMP: Bone morphogenetic protein; SMAD: Small mothers against decapentaplegic homolog.
Figure 4
Figure 4
Inhibitory effect of small mothers against decapentaplegic homolog 7 on the process of colorectal cancer development. TGF: Transforming growth factor; SMAD: Small mothers against decapentaplegic homolog.
Figure 5
Figure 5
Inhibition strategies of transforming growth factor-β signaling pathway and miRNAs targets for colorectal cancer treatment. TGF: Transforming growth factor; SMAD: Small mothers against decapentaplegic homolog.
See this image and copyright information in PMC

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