Inhibitor of Growth Factors Regulate Cellular Senescence
Abstract
:Simple Summary
Abstract
1. Introduction
2. Cell Line Studies and Experiments in Clinical Samples
2.1. ING1
2.2. ING2
2.3. ING3
2.4. ING4
2.5. ING5
2.6. Animal Studies
3. Discussion
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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ING Member | Specific Function | Redundant Function | Related Pathways | Reference |
---|---|---|---|---|
ING1 | Down-regulation of cyclin B1 and possibly cyclin E, prevention of cell transformation, and induction of apoptosis in cooperation with c-Myc | Regulation of G1/S and G2/M cell cycle transition, regulation of the p53 pathway, chromatin remodeling, and regulation of nucleotide excision repair (NER) in response to UV exposure | NF-κB, ARFMDM2-p53 | [1,2] |
ING2 | Regulation of senescence, regulation of Fas expression, and regulation of apoptosis in response to UV exposure | Regulation of the p53 pathway, regulation of NER, chromatin remodeling, and regulation of the cell cycle and apoptosis | NF-κB, TGFβ | |
ING3 | - | Regulation of the cell cycle and apoptosis, chromatin remodeling and neural development | - | |
ING4 | Inhibition of colony formation, reduction of the percentage of cells in S phase, up-regulation of Bax expression, angiogenesis, and cell migration | Regulation of the p53 pathway and chromatin remodeling | NF-κB, HIF-1α | |
ING5 | Reduction of colony-forming efficiency, inhibition of S-phase, and induction of p21 | Regulation of the p53 pathway, chromatin remodeling, and regulation of the cell cycle and apoptosis | - |
Disease/Cellular Mechanism | ING Type and Signaling Pathways | Cell Line | Function | Reference |
---|---|---|---|---|
Aging | ING1a and Rb pathway | Hs68 fibroblast cells, and EA.hy926 and HaCaT cells | ↑↑ ING1a: ↑ senescence in the absence of activating p53-mediated DNA damage signaling by activating the Rb pathway | [20] |
Breast cancer | ING5 | MDA-MB-231 and MCF-7 cells | ↑↑ ING5: ↓ cell viability, glycolysis, and mitochondrial respiration, ↑ apoptosis, S arrest, autophagy, or senescence, and ↑ chemoresistance to Cisplatin, MG132, paclitaxel, and SAHA | [44] |
Glioma | ING5 | U87 | ↑↑ ING5: ↓ proliferation, energy metabolism, migration, and invasion, and ↑ G2/M arrest, apoptosis, dedifferentiation, and senescence | [45] |
Head and neck squamous cell carcinoma | ING3, p300, p21, and p53 | HNSCC cells | ↑↑ ING3: ↑ p53-mediated cell-cycle arrest, senescence, and/or apoptosis via interacting with p300 and p21 | [38] |
Induction of apoptosis | ING1 and BAX | SKBR3; MDA-MB468, BT474, and T47D lines; HCT116, and HEK293 | The degree of mitochondrial translocation is correlated with the ability of ING1 to induce apoptosis. Binding and activation of BAX by ING1 are needed for the induction of apoptosis. | [25] |
Osteosarcoma | ING2 | HOS cells | ↑↑ ING2: ↑ apoptosis, G1 phase arrest, and senescence | [32] |
Ovarian cancer | ING5 | ES-2, H08910, H08910-PM, OVCAR3, SKOV3/DDP, A2780, and A2780/T | ↑↑ ING5: ↓ cell viability and migration, invasion, and ↑ apoptosis, cell cycle arrest, senescence, and autophagy | [46] |
Prostate cancer | ING1b, ING2, and AR signaling | LNCaP PCa cells | ∆ ING1b: ↓ growth and migration, ↑ induction of cellular senescence and the cell cycle inhibitor p16 INK4a ↑↑ ING2: causes ↑ growth arrest, and induces cellular senescence by interacting with AR and inhibiting AR transcriptional activation | [26] |
ING1b and AR signaling | ING1b knockout (KO) mouse embryonic fibroblasts (MEFs), PC3 cells, PC3-AR cell line, C4-2 cells, LNCaP, and NIH3T3 S2-6 | ↑↑ ING1b: ↑ cellular senescence, and ↓ growth and migration via inhibiting AR-mediated transactivation | [27] | |
Regulation of endocytosis | ING1a, Rb-E2F pathway, and ITSN2 | Hs68 and WI38 fibroblast cells | ↑↑ ING1a: ↑ cellular senescence to regulate endocytosis via the Rb-E2F pathway and overexpression of ITSN2 | [28] |
Tongue squamous cell carcinoma | ING5, two truncated fragments of ING5 (aa 1-184 and aa 107-226), cyclin E, and CDK2 | HSC-3 | ↑↑ ING5: ↓ proliferation and ↑ apoptosis in HSC-3 cells Two truncated fragments of ING5 (aa 1-184 and aa 107-226): ↑ cellular senescence and inhibition of cyclin E and CDK2 expression. | [47] |
Tumor Type | Animal Models | Results | Reference |
---|---|---|---|
Breast cancer | Balb/c nude mice | ↑↑ ING5: ↓ tumor volume and weight | [44] |
Glioma | Female Balb/c nude mice | ↑↑ ING5: ↓ tumor volume and weight | [45] |
Ovarian cancer | Female Balb/c nude mice | ↑↑ ING5: ↓ proliferation, and ↑ apoptosis and autophagy | [46] |
Prostate cancer | Ing1 knockout (KO) mice | ∆ ING1: ↓ endogenous AR target genes | [26] |
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Ghafouri-Fard, S.; Taheri, M.; Baniahmad, A. Inhibitor of Growth Factors Regulate Cellular Senescence. Cancers 2022, 14, 3107. https://doi.org/10.3390/cancers14133107
Ghafouri-Fard S, Taheri M, Baniahmad A. Inhibitor of Growth Factors Regulate Cellular Senescence. Cancers. 2022; 14(13):3107. https://doi.org/10.3390/cancers14133107
Chicago/Turabian StyleGhafouri-Fard, Soudeh, Mohammad Taheri, and Aria Baniahmad. 2022. "Inhibitor of Growth Factors Regulate Cellular Senescence" Cancers 14, no. 13: 3107. https://doi.org/10.3390/cancers14133107