Table 5.
Functional studies of the ATPase subunits of the CHD complexes in PDAC (or other cancers).
| CHD Subfamily | |
|---|---|
| Subunit | Protein Name/Functional Studies |
| CHD1 * | Chromodomain Helicase DNA Binding Protein 1. See Section 4.3.1. |
| CHD2 * | Chromodomain Helicase DNA Binding Protein 2. Tumor suppressor role in chronic lymphocytic leukemia [209]. Hypomethylated in PDAC [207]. Required to maintain the differentiation potential of mouse ESCs [210]. |
| CHD6 * | Chromodomain Helicase DNA Binding Protein 6. A cancer driver and key regulator of the oxidative DNA damage response [211]. |
| CHD7 * | Chromodomain Helicase DNA Binding Protein 7. See Section 4.3.3. |
| CHD8 * | Chromodomain Helicase DNA Binding Protein 8. Differentially methylated in PDAC [207]. Decreased expression in gastric cancer samples [212]. Negative regulator of the Wnt/β-catenin pathway [212,213], CHD8 knockdown in gastric cancer cells promoted proliferation [212]. |
| CHD9 * | Chromodomain Helicase DNA Binding Protein 9. Decreased expression in CRC patient samples that correlated with worse prognosis [214]. |
| CHD3 * | Chromodomain Helicase DNA Binding Protein 3. Component of the NuRD complex. Aberrant methylation was detected in advanced CRC and gastric cancer [215,216]. Overexpressed in cancers, including PDAC [216]. |
| CHD4 * | Chromodomain Helicase DNA Binding Protein 4. Component of the NuRD complex. High expression was associated with tumor status, metastasis and poor prognosis in rectal cancer [217]. In CRC, CHD4 interacted with oxidative DNA damage sites and double-strand breaks recruiting repressive chromatin proteins that maintained epigenetic silencing of tumor suppressor genes [64]; high levels of CHD4 were associated with poor prognosis [64]. CHD4 was identified as a potential therapeutic target in CRC [63,64] as knockdown of CHD4 sensitized cells to DAC-induced cell death and reactivated tumor suppressor genes [63]. |
| CHD5 | Chromodomain Helicase DNA Binding Protein 5. Component of the NuRD complex. Tumor suppressor. See Section 4.3.2. |
Note: * No/limited mechanistic studies in PDAC. Only the ATPase components are listed in the table. CHD members form multisubunit complexes [186], which are not discussed in this review.