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Review
. 2020 Dec 24;22(1):130.
doi: 10.3390/ijms22010130.

Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements

Ahmed Malki  1 , Rasha Abu ElRuz  1 , Ishita Gupta  2   3   4 , Asma Allouch  1 , Semir Vranic  2   3 , Ala-Eddin Al Moustafa  2   3   4
Affiliations
Review

Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements

Ahmed Malki et al. Int J Mol Sci. .

Abstract

Colorectal cancer (CRC), the third most common type of cancer, is the second leading cause of cancer-related mortality rates worldwide. Although modern research was able to shed light on the pathogenesis of CRC and provide enhanced screening strategies, the prevalence of CRC is still on the rise. Studies showed several cellular signaling pathways dysregulated in CRC, leading to the onset of malignant phenotypes. Therefore, analyzing signaling pathways involved in CRC metastasis is necessary to elucidate the underlying mechanism of CRC progression and pharmacotherapy. This review focused on target genes as well as various cellular signaling pathways including Wnt/β-catenin, p53, TGF-β/SMAD, NF-κB, Notch, VEGF, and JAKs/STAT3, which are associated with CRC progression and metastasis. Additionally, alternations in methylation patterns in relation with signaling pathways involved in regulating various cellular mechanisms such as cell cycle, transcription, apoptosis, and angiogenesis as well as invasion and metastasis were also reviewed. To date, understanding the genomic and epigenomic instability has identified candidate biomarkers that are validated for routine clinical use in CRC management. Nevertheless, better understanding of the onset and progression of CRC can aid in the development of early detection molecular markers and risk stratification methods to improve the clinical care of CRC patients.

Keywords: Colorectal cancer; chromosomal instability; microsatellite instability; molecular pathways; therapeutics.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Multistep genetic model for colorectal adenocarcinoma sequence. There are three pathways regulating the adenocarcinoma sequence: chromosomal instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP) hypermethylation.
Figure 2
Figure 2
Schematic representation of the molecular pathways involved in CRC pathogenesis.
See this image and copyright information in PMC

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