The KEAP1-NRF2 System as a Molecular Target of Cancer Treatment
The Kelch-like ECH-associated protein (KEAP1)- Nuclear factor erythroid-derived 2-like 2 (encoded by the gene; NRF2) system attracts extensive interest from scientists in basic and clinical cancer research fields, as NRF2 exhibits activity as both an oncogene and tumor suppressor, depending on the c...
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| Veröffentlicht in: | Cancers 2020-12, Vol.13 (1), p.46 |
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| creator | Taguchi, Keiko Yamamoto, Masayuki |
| description | The Kelch-like ECH-associated protein (KEAP1)- Nuclear factor erythroid-derived 2-like 2 (encoded by the
gene; NRF2) system attracts extensive interest from scientists in basic and clinical cancer research fields, as NRF2 exhibits activity as both an oncogene and tumor suppressor, depending on the context. Especially unique and malignant, NRF2-addicted cancers exhibit high levels of NRF2 expression. Somatic mutations identified in the
or
genes of NRF2-addicted cancers cause the stabilization and accumulation of NRF2. NRF2-addicted cancers hijack the intrinsic roles that NRF2 plays in cytoprotection, including antioxidative and anti-electrophilic responses, as well as metabolic reprogramming, and acquire a marked advantage to survive under severe and limited microenvironments. Therefore, NRF2 inhibitors are expected to have therapeutic effects in patients with NRF2-addicted cancers. In contrast, NRF2 activation in host immune cells exerts significant suppression of cancer cell growth, indicating that NRF2 inducers also have the potential to be therapeutics for cancers. Thus, the KEAP1-NRF2 system makes a broad range of contributions to both cancer development and suppression. These observations thus demonstrate that both NRF2 inhibitors and inducers are useful for the treatment of cancers with high NRF2 activity. |
| doi_str_mv | 10.3390/cancers13010046 |
| format | Article |
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or
genes of NRF2-addicted cancers cause the stabilization and accumulation of NRF2. NRF2-addicted cancers hijack the intrinsic roles that NRF2 plays in cytoprotection, including antioxidative and anti-electrophilic responses, as well as metabolic reprogramming, and acquire a marked advantage to survive under severe and limited microenvironments. Therefore, NRF2 inhibitors are expected to have therapeutic effects in patients with NRF2-addicted cancers. In contrast, NRF2 activation in host immune cells exerts significant suppression of cancer cell growth, indicating that NRF2 inducers also have the potential to be therapeutics for cancers. Thus, the KEAP1-NRF2 system makes a broad range of contributions to both cancer development and suppression. These observations thus demonstrate that both NRF2 inhibitors and inducers are useful for the treatment of cancers with high NRF2 activity.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13010046</identifier><identifier>PMID: 33375248</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Autophagy ; Cancer ; Cancer therapies ; Cell activation ; Cell cycle ; Cytokines ; Enzymes ; Gene expression ; Kinases ; Microenvironments ; NRF2 protein ; Phosphorylation ; Pollutants ; Proteins ; Review ; Transcription factors ; Tumor suppressor genes</subject><ispartof>Cancers, 2020-12, Vol.13 (1), p.46</ispartof><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-51fa51304d11d4b11c0414f7db3eecfe33cb3cfc5e6b18db1ea79964fb1c1cdb3</citedby><cites>FETCH-LOGICAL-c487t-51fa51304d11d4b11c0414f7db3eecfe33cb3cfc5e6b18db1ea79964fb1c1cdb3</cites><orcidid>0000-0002-5798-0076</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795874/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795874/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33375248$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Taguchi, Keiko</creatorcontrib><creatorcontrib>Yamamoto, Masayuki</creatorcontrib><title>The KEAP1-NRF2 System as a Molecular Target of Cancer Treatment</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>The Kelch-like ECH-associated protein (KEAP1)- Nuclear factor erythroid-derived 2-like 2 (encoded by the
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or
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These observations thus demonstrate that both NRF2 inhibitors and inducers are useful for the treatment of cancers with high NRF2 activity.</description><subject>Autophagy</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell activation</subject><subject>Cell cycle</subject><subject>Cytokines</subject><subject>Enzymes</subject><subject>Gene expression</subject><subject>Kinases</subject><subject>Microenvironments</subject><subject>NRF2 protein</subject><subject>Phosphorylation</subject><subject>Pollutants</subject><subject>Proteins</subject><subject>Review</subject><subject>Transcription factors</subject><subject>Tumor suppressor genes</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkU1PwzAMhiMEYhPszA1F4sKlLKnTpr2A0LQB4lMwzlGaumNTP0bSIu3fE2BMMF9syY9f23oJOeLsDCBlQ6Nrg9ZxYJwxEe-QfshkGMRxKnb_1D0ycG7BfABwGct90gMAGYUi6ZOL6RvS2_HlEw8enichfVm5FiuqHdX0vinRdKW2dKrtDFvaFHT0vZNOLeq2wro9JHuFLh0O1vmAvE7G09F1cPd4dTO6vAuMSGQbRLzQkT9U5JznIuPcMMFFIfMMEE2BACYDU5gI44wnecZRyzSNRZFxw42nDsj5j-6yyyrMjV9tdamWdl5pu1KNnqv_nXr-pmbNh5IyjRIpvMDpWsA27x26VlVzZ7AsdY1N51QoJCRpGkHs0ZMtdNF0tvbvfVECojQE5qnhD2Vs45zFYnMMZ-rLH7Xlj584_vvDhv91Az4BeaiLsg</recordid><startdate>20201226</startdate><enddate>20201226</enddate><creator>Taguchi, Keiko</creator><creator>Yamamoto, Masayuki</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5798-0076</orcidid></search><sort><creationdate>20201226</creationdate><title>The KEAP1-NRF2 System as a Molecular Target of Cancer Treatment</title><author>Taguchi, Keiko ; 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or
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| source | MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central; EZB Electronic Journals Library; PubMed Central Open Access |
| subjects | Autophagy Cancer Cancer therapies Cell activation Cell cycle Cytokines Enzymes Gene expression Kinases Microenvironments NRF2 protein Phosphorylation Pollutants Proteins Review Transcription factors Tumor suppressor genes |
| title | The KEAP1-NRF2 System as a Molecular Target of Cancer Treatment |
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