p53/p73 Protein Network in Colorectal Cancer and Other Human Malignancies
Abstract
:Simple Summary
Abstract
1. Introduction
2. Gene Architecture and Generation of the p53/p73 Isoforms
3. Structure of the p53 Protein Isoforms
4. Structure of the p73 Protein Isoforms
5. Regulation of the p53 Isoforms’ Expression and Activity
6. Regulation of the p73 Isoforms’ Expression and Activity
7. Biological Activity and Functions of the p53 Isoforms
8. Biological Activity and Functions of the p73 Isoforms
9. Crosstalk between p53/p73 Isoforms
10. Alterations of the p53 and p73 Isoforms in Cancer
11. Alterations of the p53/p73 Isoforms Expression in Colorectal Cancer
12. Involvement of the p53/p73 Isoforms in CRC Development and Progression
13. Prognostic Relevance of the p53/p73 Isoforms Expression in CRC
14. Targeting the p53/p73 Family Isoforms in CRC
15. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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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 |
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Horvat, A.; Tadijan, A.; Vlašić, I.; Slade, N. p53/p73 Protein Network in Colorectal Cancer and Other Human Malignancies. Cancers 2021, 13, 2885. https://doi.org/10.3390/cancers13122885
Horvat A, Tadijan A, Vlašić I, Slade N. p53/p73 Protein Network in Colorectal Cancer and Other Human Malignancies. Cancers. 2021; 13(12):2885. https://doi.org/10.3390/cancers13122885
Chicago/Turabian StyleHorvat, Anđela, Ana Tadijan, Ignacija Vlašić, and Neda Slade. 2021. "p53/p73 Protein Network in Colorectal Cancer and Other Human Malignancies" Cancers 13, no. 12: 2885. https://doi.org/10.3390/cancers13122885