Gain-of-Function Mutations in p53 in Cancer Invasiveness and Metastasis
Abstract
:1. Introduction
2. Animal Models of p53 GOF Mutations
3. Epithelial–Mesenchymal Transition and Related Phenotypes
4. Inflammation, Chemokines, and Invasiveness
5. Metabolic Alterations and Invasiveness
6. Concluding Remarks
Author Contributions
Funding
Conflicts of Interest
Abbreviations
GOF | Gain-of-function |
EMT | Epithelial–mesenchymal transition |
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Reference | p53 Variant | Phenotype | Molecular Mechanism |
---|---|---|---|
(Godfrey et al., 2018) [56] | R172H | Invasiveness | miR-142 downregulation by Dnmt1-mediated DNA hypermethylation |
(Kogan-Sakin et al., 2011) [34] | R175H | EMT induction | TWIST1 upregulation |
(Ali et al., 2014) [36] | R175H | Increased cellular mobility, decreased apoptosis, chemoresistance | KLF17 sequestration |
(Dong et al., 2013) [46] | R175H | EMT induction | miR-130b repression, (miR130b-ZEB1 axis) |
(Ji et al., 2015) [50] | R175H | Activation of pro-oncogenic signaling | Selective Smad3 binding, Smad2/3 imbalance |
(Weissmueller et al., 2014) [54] | R175H R272H | Metastasis | PDGFRB upregulation through p73/NF-Y |
(Shakya et al., 2017) [55] | R175H, R248Q, R273H | Invasiveness | A1AT upregulation |
(Cooks et al., 2018) [59] | R175H, R248W, R273H | Tumor growth | Macrophage reprograming by exosomes with miR-1246 |
(Tanaka et al., 2018) [37] | G245D | Invasiveness EMT induction | FOXO3a downregulation FOXM1 derepression |
(Nielsen et al., 2013) [47] | R248Q R282W | Metastasis, invasiveness | p63 sequestration, (miR-155 upregulation) |
Vogiatzi et al., 2016) [51] | R248W, R273H, R280K | Tumor progression and metastasis | Endoplasmic Reticulum UDPase ENTPD5 upregulation |
(Tan et al., 2015) [39] | R273H | Cell survival and anoikis resistance | AKT-dependent suppression of BCL2-modifying factor (BMF) |
(Chryplewicz et al., 2019) [41] | R273H | Metastasis, invasiveness, migration | APA6 downregulation, leading to LPA accumulation |
(Subramanian et al., 2015) [48] | R273H | Metastasis, invasiveness | let-7i downregulation |
(Datta et al., 2019) [49] | R273H | Metastasis | miR-132 and miR-147b |
(Zhao et al., 2019) [58] | R273H | Cell migration, chemoresistance, proliferation | lnc273-31 and lnc273-34 upregulation |
(Ju et al., 2019) [60] | R273H | EMT induction | Exosomes containing miR-21 and miR-769 increased TGF-β production in fibroblasts |
(Adorno et al., 2009) [53] | R280K | Cell migration, invasiveness and metastasis | SMAD2/3, Ras (p63 inhibition) |
Reference | p53 Variant | Phenotype | Molecular Mechanism |
---|---|---|---|
(Zhang et al., 2018) [75] | R172H | Metastasis | CXCL5-MAPK signaling pathway upregulation by PLAC8 (onzin) |
(Yan & Chen, 2009) [81] | R175H | Chemoresistance | Direct CXCL1 upregulation |
(Yeudall et al., 2012) [74] | R175H, R273H | Cell motility, metastasis | CXCL5, CXCL8 and CXCL12 upregulation by NF-κB |
(Vaughan et al., 2012) [79] | R175H, R273H | Increased motility and invasiveness | Receptor protein tyrosine kinase AXL upregulation |
(Di Minin et al., 2014) [70] | R175H, R273H, R280K | Invasiveness, inflammation | DAB2IP inhibition |
(Fontemaggi et al., 2009) [80] | R175H, R273H, R280K | Neoangiogenesis | CXCL8 and CXCL1 upregulation by E2F1 |
(Cooks et al., 2013) [67] | R248W | Chronic inflammation- invasiveness, metastasis | NF-κB activation by TNF-α |
(Rahnamoun et al., 2017) [73] | R273H | Cancer-promoting gene expression | NF-κB |
(Rahnamoun et al., 2018) [77] | R273H | Invasiveness | MMP9 and CCL2 upregulation by MLL4 |
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Roszkowska, K.A.; Gizinski, S.; Sady, M.; Gajewski, Z.; Olszewski, M.B. Gain-of-Function Mutations in p53 in Cancer Invasiveness and Metastasis. Int. J. Mol. Sci. 2020, 21, 1334. https://doi.org/10.3390/ijms21041334
Roszkowska KA, Gizinski S, Sady M, Gajewski Z, Olszewski MB. Gain-of-Function Mutations in p53 in Cancer Invasiveness and Metastasis. International Journal of Molecular Sciences. 2020; 21(4):1334. https://doi.org/10.3390/ijms21041334
Chicago/Turabian StyleRoszkowska, Katarzyna A., Slawomir Gizinski, Maria Sady, Zdzislaw Gajewski, and Maciej B. Olszewski. 2020. "Gain-of-Function Mutations in p53 in Cancer Invasiveness and Metastasis" International Journal of Molecular Sciences 21, no. 4: 1334. https://doi.org/10.3390/ijms21041334