Hallmark of Cancer: Enabling replicative immortality through non-genotoxic carcinogens (Homo sapiens)
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Description
This pathway shows the effect of non-genotoxic carcinogens on inducing the hallmark of cancer: Enabling replicative immortality. Normal cells are no longer able do dived after a certain amount of divisions (Hick’s limit), after which they either die or enter senescence. The enabling replicative immortality hallmark gives the capacity to cancer cells to divide an infinite amount of times.
The main mechanism stopping the cells from dividing is the reduction in telomeres, they are ‘caps’ at the end of chromosomes that decrease in size after every division. Therefore, the main mechanism influenced by this hallmark is the protein able to restore the telomeres, telomerase. A component of telomerase is TERT which is shown in the pathway. This pathway is affected in the nucleus and the methylation status of certain genes are important. The clarification of the effect of the methylation status is written when double clicking the gene. In addition to repairing the telomeres, the TERT sub-unit and telomerases have other functions which are also portrayed in the pathway. Another mechanism to enable replicative immortality is the by-pass senescence. This is triggered by nickel and nickel-derivates and shown on the right side of the pathways.
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Ontology Terms
Saving...Bibliography
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- Liu, Z., Li, Q., Li, K., et al.; ''Telomerase reverse transcriptase promotes epithelial–mesenchymal transition and stem cell-like traits in cancer cells''; Oncogene 32, 2013
- Takayanagi S, Tokunaga T, Liu X, Okada H, Matsushima A, Shimohigashi Y; ''Endocrine disruptor bisphenol A strongly binds to human estrogen-related receptor gamma (ERRgamma) with high constitutive activity.''; Toxicol Lett, 2006 PubMed Europe PMC Scholia
- Rayess H, Wang MB, Srivatsan ES; ''Cellular senescence and tumor suppressor gene p16.''; Int J Cancer, 2012 PubMed Europe PMC Scholia
- Dratwa M, Wysoczańska B, Łacina P, Kubik T, Bogunia-Kubik K; ''TERT-Regulation and Roles in Cancer Formation.''; Front Immunol, 2020 PubMed Europe PMC Scholia
- Carnero A, Blanco-Aparicio C, Kondoh H, Lleonart ME, Martinez-Leal JF, Mondello C, Scovassi AI, Bisson WH, Amedei A, Roy R, Woodrick J, Colacci A, Vaccari M, Raju J, Al-Mulla F, Al-Temaimi R, Salem HK, Memeo L, Forte S, Singh N, Hamid RA, Ryan EP, Brown DG, Wise JP Sr, Wise SS, Yasaei H; ''Disruptive chemicals, senescence and immortality.''; Carcinogenesis, 2015 PubMed Europe PMC Scholia
- Ghosh A, Saginc G, Leow SC, Khattar E, Shin EM, Yan TD, Wong M, Zhang Z, Li G, Sung WK, Zhou J, Chng WJ, Li S, Liu E, Tergaonkar V; ''Telomerase directly regulates NF-κB-dependent transcription.''; Nat Cell Biol, 2012 PubMed Europe PMC Scholia
- Zhou L, Zheng D, Wang M, Cong YS; ''Telomerase reverse transcriptase activates the expression of vascular endothelial growth factor independent of telomerase activity.''; Biochem Biophys Res Commun, 2009 PubMed Europe PMC Scholia
- Takahashi A, Higashino F, Aoyagi M, Kyo S, Nakata T, Noda M, Shindoh M, Kohgo T, Sano H; ''Bisphenol A from dental polycarbonate crown upregulates the expression of hTERT.''; J Biomed Mater Res B Appl Biomater, 2004 PubMed Europe PMC Scholia
- Bermudez Y, Yang H, Saunders BO, Cheng JQ, Nicosia SV, Kruk PA; ''VEGF- and LPA-induced telomerase in human ovarian cancer cells is Sp1-dependent.''; Gynecol Oncol, 2007 PubMed Europe PMC Scholia
History
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External references
DataNodes
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| Name | Type | Database reference | Comment |
|---|---|---|---|
| B-catenin | GeneProduct | ENSG00000168036 (Ensembl)  | |
| BPA | Metabolite | CHEBI:33216 (ChEBI) | |
| CDK4 | GeneProduct | ENSG00000135446 (Ensembl) | |
| CDKN2A | GeneProduct | ENSG00000147889 (Ensembl) | |
| Cyclin D1 | GeneProduct | ENSG00000110092 (Ensembl) | |
| E2F1 | GeneProduct | ENSG00000101412 (Ensembl) | |
| ESR1 | GeneProduct | ENSG00000091831 (Ensembl) | |
| H3K27me3 | Protein | ||
| IL6 | GeneProduct | ENSG00000136244 (Ensembl) | |
| NFKB | GeneProduct | ENSG00000109320 (Ensembl) | |
| RB1 | GeneProduct | ENSG00000139687 (Ensembl) | |
| TERT promotor | GeneProduct |
| |
| TERT | GeneProduct | 7015 (Entrez Gene) | |
| THOR | GeneProduct |
| |
| TNF | GeneProduct | ENSG00000232810 (Ensembl) | |
| Telomerase | GeneProduct | ENSG00000277925 (Ensembl) | |
| VEGF | GeneProduct | 7422 (Entrez Gene) | |
| nickel and derivates | Metabolite | CHEBI:28112 (ChEBI) | |
| p16 | GeneProduct | ENSG00000147889 (Ensembl) | |
| unknown Non-genotoxic carcinogen | Metabolite |
Annotated Interactions
No annotated interactions
