Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements
Abstract
:1. Introduction
2. Molecular Basis of Colorectal Cancer
2.1. Chromosomal Instability (CIN) Pathway
2.1.1. Adenomatous Polyposis Coli (APC) Gene and Wnt Signaling Pathway
2.1.2. TP53 Pathway
2.1.3. The 18q Loss of Heterozygosity (LOH)
2.2. The Microsatellite Instability Pathway
2.3. CpG Island Methylator Phenotype (CIMP) Pathway
EGFR-KRAS-BRAF Pathway
3. Therapeutic Strategies
3.1. Targeting CIN Pathway
3.2. Targeting MSI Pathway
3.3. Targeting CIMP Pathway
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
5-FU | Fluorouracil |
ACVR2 | Activin receptor type 2 |
AFAP | Attenuated familial adenomatous polyposis |
ALP | Alpelisib |
AMPK | Adenosine monophosphate-activated protein kinase |
APC | Adenomatous polyposis coli |
BRAF | Serine/threonine-protein kinase B-Raf |
Bub | Budding uninhibited by benzimidazoles |
CDC20 | Cell division cycle 20 |
CDKN | Cyclin-dependent kinases |
CIMP | CpG island methylator phenotype |
CIN | Chromosomal instability |
CMS | Consensus molecular subtypes |
COX | Cyclooxygenase |
CRC | Colorectal cancer |
CTNNB1 | Catenin beta-1 |
DCC | Deleted in colorectal cancer |
dMMR | Defective mismatch repair |
EDM | Exonuclease domain |
EGFR | Epidermal growth factor receptor |
ERK | Extracellular signal related kinase |
FAP | Familial adenomatous polyposis |
FDA | Food and Drug Administration |
FOLFOX | Folinic acid, fluorouracil, and oxaliplatin |
GSH | Glutathione |
GSK3-β | Glycogen synthase kinase 3-β |
HNPCC | Hereditary non-polyposis colorectal cancer |
IBD | Inflammatory bowel disease; Ig: Immunoglobin |
IGFBP7 | Insulin-like growth factor-binding protein 7 |
JAK | Janus kinase |
KRAS | Kirsten ras |
LOH | Loss of heterozygosity |
LV | Leucovorin |
MAP | MUTYH-associated polyposis |
MAP/MEK | Mitogen-activated protein kinase |
MLH/MSH | MutL homolog |
MSI | Microsatellite instability |
MSS | Microsatellite stable |
NF-κB | Nuclear factor kappa |
NSAIDs | Non-steroidal anti-inflammatory drugs |
OS | Overall survival |
PD-1/PD-L1 | Programmed death ligand-1 |
PI3K | Phosphatidylinositol 3-kinase |
PI3KCA | Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha |
POLE/POLD1 | Polymerase epsilon or delta 1 |
RAC1 | Rac family small GTPase 1 |
ROS | Reactive oxygen species |
SCNAs | Somatic copy number alterations |
SMAD | Small mothers against decapentaplegic |
STAT | Signal transducer and activator of transcription |
TCGA | The Cancer Genome Atlas |
TGF-β | Transforming growth factor-β |
TIGAR | T53-induced glycolysis regulatory phosphatase |
TNM | Tumor-nodes-metastasis |
TP53 | Tumor protein 53 |
TSG | Tumor suppressor gene |
VEGF | Vascular endothelial growth factor |
VEGFR | Vascular endothelial growth factor receptor |
Wnt | Wingless |
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Subtype | Gene Expression | Prognosis | Reference |
---|---|---|---|
CMS1 (MSI immune) |
| Very poor survival rate after relapse | [4] |
CMS2 (Canonical) |
| Better survival rate after relapse in comparison to other subtypes | |
CMS3 (Metabolic) |
| Better survival rate after relapse in comparison to other subtypes | |
CMS4 (Mesenchymal) |
| Worse overall and relapse-free survival as compared to other subtypes |
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Malki, A.; ElRuz, R.A.; Gupta, I.; Allouch, A.; Vranic, S.; Al Moustafa, A.-E. Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements. Int. J. Mol. Sci. 2021, 22, 130. https://doi.org/10.3390/ijms22010130
Malki A, ElRuz RA, Gupta I, Allouch A, Vranic S, Al Moustafa A-E. Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements. International Journal of Molecular Sciences. 2021; 22(1):130. https://doi.org/10.3390/ijms22010130
Chicago/Turabian StyleMalki, Ahmed, Rasha Abu ElRuz, Ishita Gupta, Asma Allouch, Semir Vranic, and Ala-Eddin Al Moustafa. 2021. "Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements" International Journal of Molecular Sciences 22, no. 1: 130. https://doi.org/10.3390/ijms22010130
APA StyleMalki, A., ElRuz, R. A., Gupta, I., Allouch, A., Vranic, S., & Al Moustafa, A.-E. (2021). Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements. International Journal of Molecular Sciences, 22(1), 130. https://doi.org/10.3390/ijms22010130