Table 1.
Representative Genes Commonly Methylated and Silenced in Colorectal Cancer
| Gene | Protein | Function* | Effect of Loss of Function |
|---|---|---|---|
| APC | Adenomatous polyposis coli | Wnt signaling pathway inhibition | Increased Wnt/β-catenin signaling |
| MLH1 | MutL homolog 1 | DNA Mismatch repair | Microsatellite instability |
| MGMT | O-6-methylguanine-DNA methyltransferase | Repair of alkylation DNA damage | Increased G→A mutation frequency |
| RASSF1A | Ras association domain family 1 (isoform A) | Negative RAS effector, pro-apoptotic, microtubule stablization | Increased RAS/RAF/MAP kinase signaling, death receptor-dependent apoptosis |
| SLC5A8 | Sodium solute symporter family 5 member 8 | Sodium and short chain fatty acid transporter, suppresses colony formation | ? |
| RUNX3 | Runt-related transcription factor 3 | Transcription factor | Decreased TGF-β/BMP signaling |
| MINT1** | Methylated in tumor locus 3 | NA | NA |
| MINT31** | Methylated in tumor locus 31 | NA | NA |
| SFRP1 | Secreted frizzled-related protein 1 | Wnt antagonist | Increased Wnt/β-catenin signaling |
| SFRP2 | Secreted frizzled-related protein 2 | Wnt antagonist | Increased Wnt/β-catenin signaling |
| CDH1 | E-Cadherin | Calcium dependent cell-cell adhesion glycoprotein | Loss of cell adhesion, possible increased Wnt/β-catenin signaling |
| CDH13 | Cadherin 13 | Selective cell recognition and adhesion, anti-apoptotic | Increased PI3K/Akt/mTOR signaling, MAPK signaling |
| CRABP1 | Retinol-binding protein 1 | Carrier protein for transport of retinol, promotes apoptosis | ? |
| CDKN2A/p16 | Cyclin-dependent kinase inhibitor 2A | Regulates cell cycle G1 progression | Increased cell proliferation |
| HLTF | Helicase-like transcription factor | dsDNA translocase, fork remodeling activity, ubiquitin ligase | Impaired DNA repair |
| CDKN2A (P14, ARF) | Protein 14 | Inhibits E3 ubiquitin ligase | Decreased p53 stabilization and activation |
| ESR1 | Estrogen receptor 1 | Ligand-activated transcription factor | Loss of estrogen receptor signaling |
| TIMP3 | Tissue inhibitor of metalloproteinase 3 | Inhibition of MMPs and ADAMs | Increased EGF receptor signaling, TNFalpha signaling |
| CXCL12 | Chemokine (C-X-C motif) ligand 12 | Alpha chemokine | Increased tumor cell metastases |
| ID4 | Inhibitor of DNA binding 4 | Transcription factor | ? |
| IRF8 | Interferon regulatory factor 8 | Transcription factor | Interferon signaling |
| THBS1/TSP1 | Thrombospondin 1 | Cell-to-cell and cell-to-matrix adhesive glycoprotein | Decreased TGF-β1 signaling |
| DAPK | Death associated protein kinase | Induction of cell death | Interferon gamma signaling, TNF alpha signaling, Fas/APO1 signaling |
| VIM | Vimentin | Stablizing cytoskeleton | No known biological effect |
| SEPT9 | Septin 9 | GTPase, formation of filaments | Impaired Cytokinesis and loss of cell cycle control |
*
Many of these gene products have multiple functions. The listed function in this table is the one most commonly cited as the one responsible for colorectal cancer formation.
**
MINTs are Methylated IN Tumor loci, and are not specific genes.