Table 1.
Involvement of the p53/p73 isoforms in colorectal cancer development and progression. The p53/p73 family of isoforms is associated with a plethora of cancer-related cellular functions such as apoptosis and sensitivity to drugs, DNA repair, autophagy, proliferation, inflammation, invasion, angiogenesis, metabolism, and senescence.
| Cellular Function | Isoform | Model | Signalling | Effect | Reference |
|---|---|---|---|---|---|
| Apoptosis and sensitivity to antitumor drugs | ∆40p53 | HCT116−/− | ↑ miR-186 → ↓ YY1 |
↓ proliferation | [187] |
| ∆133p53ß | HCT116, SW480, LoVo, SW620 and Colo205 | ↓ RhoB | ↑ resistance to camptothecin-induced apoptosis | [175] | |
| TAp73, ∆Np73, ∆Ex2p73, ∆Ex2/3p73 | SW480-ADH and HCT116 | ↑ survivin → ↑ p73 isoforms |
- | [299] | |
| TAp73 | HCT116 p53−/− and p53-mt HT-29 |
Casp3 and PARP cleavage | ↑ bortezomib-induced apoptosis | [300] | |
| ΔNp73 | HCT116 | - | ↑ proliferation and resistance to oxaliplatin-induced apoptosis | [293] | |
| ΔNp73 | DLD1 and HCT116 | - | ↑ colonosphere formation and resistance to prodigiosin | [301] | |
| ΔNp73α | HCT116 and HCT116 xenograft | - | = cellular and tumor growth = sensitivity to cDDP or DX in vitro and in vivo |
[302,303] | |
| ΔNp73α | HCT116 p53−/− | - | = cellular growth = sensitivity to cDDP, DX and UV light |
[304] | |
| ΔNp73β | HCT116 and HCT116 p53−/− | - | ↑ cellular viability = sensitivity to cDDP |
[305] | |
| Exosomal ΔNp73β | HCT116 and HCT116 xenografts | ↑ ΔNp73β mRNA in recipient cells | ↑ proliferation and resistance to oxaliplatin in vitro ↑ proliferation and tumor size |
[292] | |
| Autophagy | Δ40p53 | HCT116 | ↓ PKR/ Eif2 and DRAM | ↓ starvation and methyl methane sulfonate-induced autophagy | [186] |
| DNA repair | Δ133p53 and TAp73α | HCT116 | ↑ RAD51, LIG4 and RAD52 | DNA double-strand break repair upon γ-irradiation | [180] |
| Inflammation | Δ133p53 | HCT116 | ↑ IL-6, IL-8, Bcl-2 | - | [93] |
| Invasion | ∆133p53 and Δ133p53β | HCT116, LoVo, SW480, SW620, Colo205 | ↓ E-cadherin and β1-integrin | ↑ invasion ↑ rounded phenotype ↓ adhesion ↑ epithelial–amoeboid transition |
[192] |
| Δ133p53α, Δ133p53β and Δ133p53γ | HCT116 | ↑ RhoA and ROCKA | ↑ invasion ↑ rounded phenotype |
[188] | |
| Angiogenesis | TAp73, ΔNp73 | CRC patient samples | Correlations with VEGF and VEGF165b | - | [306] |
| ∆Ex2/3p73 | Correlation with VEGF165b | ||||
| ∆Ex2p73 | Correlations with VEGF and VEGF165b Inverse correlation with PEDF |
||||
| Metabolism | p53 and Δ40p53 | HCT116 and A549 | Glucose starvation → ↑SMAR1 ↑ IRES ↑ TIGAR |
- | [109] |
| TAp73 | HCT116 and HCT116 p53−/− | ↑ G6PD | ↑ proliferation | [307,308] | |
| TAp63 | Patient-derived CCSCs | - | ↑ glycolytic activity | [309] | |
| Senescence | ↑ p53β and ↓ Δ133p53 | CRA patient samples | - | ↑ senescence | [19] |
| ↓ p53β and ↑ Δ133p53 | CRC patient samples | Escape from senescence barrier |
↓, decreased activity, expression, or effect; ↑, increased activity, expression, or effect; →, leads to; =, unchanged; Casp3, caspase 3; CCSCs, colon cancer stem cells; cDDP, cis-diammine-dichloro-platinum; CRA, colorectal adenoma; CRC, colorectal carcinoma; DRAM, damage-regulated autophagy modulator 1; DX, doxorubicin; Eif2, eukaryotic initiation factor 2; G6PD, glucose-6-phosphate dehydrogenase; LIG4, DNA ligase 4; IL-6, interleukin 6; IL-8, interleukin 8; IRES, internal ribosome entry site; PEDF, pigment epithelium-derived factor; PKR, protein kinase R; RhoB, Ras homolog family member B; TIGAR, TP53-induced glycolysis regulatory phosphatase; VEGF, vascular endothelial growth factor.