Hallmark of Cancer: Enabling replicative immortality through non-genotoxic carcinogens (Homo sapiens)

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<?xml version="1.0" encoding="UTF-8"?> <Pathway xmlns="http://pathvisio.org/GPML/2013a" Name="Hallmark of Cancer: Enabling replicative immortality through non-genotoxic carcinogens" Version="20250428" Organism="Homo sapiens"> <Comment Source="WikiPathways-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. 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rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Telomerase reverse transcriptase promotes epithelial–mesenchymal transition and stem cell-like traits in cancer cells</bp:TITLE> <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Oncogene 32</bp:SOURCE> <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2013</bp:YEAR> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Liu, Z.</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Li, Q.</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Li, K.</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">et al.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="b4f"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">17049190</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Endocrine disruptor bisphenol A strongly binds to human estrogen-related receptor gamma (ERRgamma) with high constitutive activity.</bp:TITLE> <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Toxicol Lett</bp:SOURCE> <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2006</bp:YEAR> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Takayanagi S</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Tokunaga T</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Liu X</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Okada H</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Matsushima A</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Shimohigashi Y</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="acc"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">22025288</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cellular senescence and tumor suppressor gene p16.</bp:TITLE> <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Int J Cancer</bp:SOURCE> <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2012</bp:YEAR> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Rayess H</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Wang MB</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Srivatsan ES</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="a21"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">33329574</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">TERT-Regulation and Roles in Cancer Formation.</bp:TITLE> <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Front Immunol</bp:SOURCE> <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2020</bp:YEAR> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Dratwa M</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Wysoczańska B</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Łacina P</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Kubik T</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Bogunia-Kubik K</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="c0a"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">26106138</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Disruptive chemicals, senescence and immortality.</bp:TITLE> <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Carcinogenesis</bp:SOURCE> <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2015</bp:YEAR> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Carnero A</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Blanco-Aparicio C</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Kondoh H</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Lleonart ME</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Martinez-Leal JF</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Mondello C</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Scovassi AI</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Bisson WH</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Amedei A</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Roy R</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Woodrick J</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Colacci A</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Vaccari M</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Raju J</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Al-Mulla F</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Al-Temaimi R</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Salem HK</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Memeo L</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Forte S</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Singh N</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Hamid RA</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Ryan EP</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Brown DG</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Wise JP Sr</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Wise SS</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Yasaei H</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="e48"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">23159929</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Telomerase directly regulates NF-κB-dependent transcription.</bp:TITLE> <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Nat Cell Biol</bp:SOURCE> <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2012</bp:YEAR> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Ghosh A</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Saginc G</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Leow SC</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Khattar E</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Shin EM</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Yan TD</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Wong M</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Zhang Z</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Li G</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Sung WK</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Zhou J</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Chng WJ</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Li S</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Liu E</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Tergaonkar V</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="afc"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">19559675</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Telomerase reverse transcriptase activates the expression of vascular endothelial growth factor independent of telomerase activity.</bp:TITLE> <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Biochem Biophys Res Commun</bp:SOURCE> <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2009</bp:YEAR> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Zhou L</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Zheng D</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Wang M</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cong YS</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="c0e"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">15368248</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Bisphenol A from dental polycarbonate crown upregulates the expression of hTERT.</bp:TITLE> <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">J Biomed Mater Res B Appl Biomater</bp:SOURCE> <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2004</bp:YEAR> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Takahashi A</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Higashino F</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Aoyagi M</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Kyo S</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Nakata T</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Noda M</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Shindoh M</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Kohgo T</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Sano H</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="e7e"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">17559911</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">VEGF- and LPA-induced telomerase in human ovarian cancer cells is Sp1-dependent.</bp:TITLE> <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Gynecol Oncol</bp:SOURCE> <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2007</bp:YEAR> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Bermudez Y</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Yang H</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Saunders BO</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cheng JQ</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Nicosia SV</bp:AUTHORS> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Kruk PA</bp:AUTHORS> </bp:PublicationXref> <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#"><bp:TERM>cancer 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