The impact of oncogenic RAS on redox balance and implications for cancer development
The RAS family of proto-oncogenes comprises HRAS , KRAS , and NRAS , which are among the most mutated genes in human cancers. The RAS family genes encode small GTPases that coordinate key signaling pathways in response to growth factors. Mutations in RAS result in a constitutively active form of the...
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| creator | Lim, Jonathan K. M. Leprivier, Gabriel |
| description | The
RAS
family of proto-oncogenes comprises
HRAS
,
KRAS
, and
NRAS
, which are among the most mutated genes in human cancers. The
RAS
family genes encode small GTPases that coordinate key signaling pathways in response to growth factors. Mutations in
RAS
result in a constitutively active form of the protein that supports cellular transformation and tumorigenesis. The mechanisms of oncogenic RAS-mediated transformation encompass uncontrolled proliferation and inhibition of cell death through overactivation of the RAF-MEK-ERK and the PI3K-AKT pathways, respectively. In addition, the control of redox balance by RAS has also been proposed to play a role in its oncogenic properties. However, the exact role of redox balance in mediating mutant RAS transformation is still under debate. Here, we present, on one hand, the involvement of pro-oxidant components in oncogenic RAS transformation, such as NADPH oxidases and mitochondrial reactive oxygen species, and how these promote transformation. On the other hand, we describe the contribution of antioxidant components to mutant RAS transformation, including Nrf2, glutathione biosynthesis and xCT, as well as the mechanisms by which antioxidant programs drive transformation. Finally, we aim to reconcile the seemingly opposite effects of oncogenic RAS on redox balance and discuss a model for the complementary role of both pro-oxidant and antioxidant pathways in mutant RAS-driven tumor progression. |
| doi_str_mv | 10.1038/s41419-019-2192-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6920345</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2328304690</sourcerecordid><originalsourceid>FETCH-LOGICAL-c536t-45985990581da205452059e1145d8b22db99b39607471ce8a87741fb7900de483</originalsourceid><addsrcrecordid>eNp1UU1LAzEUDKJYqf0BXiTgeTWfu8lFKMUvKAhazyGbzbZbtklNtsX-e1Naaz0YSF7CzJt5ZAC4wugWIyruIsMMywylTbAk2eYEXBDEcMaEkKdH9x4YxDhHaVGKCM_PQY9iwYkQ7AJMJjMLm8VSmw76Gnpn_NS6xsC34Xt6wWAr_wVL3WpnLNSu2pLbxuiu8S7C2gdotlCAlV3b1i8X1nWX4KzWbbSDfe2Dj8eHyeg5G78-vYyG48xwmncZ41JwKREXuNIEccbTIS3GjFeiJKQqpSypzFHBCmys0KIoGK7LQiJUWSZoH9zvdJercmErk6yDbtUyNAsdNsrrRv1FXDNTU79WuSSIMp4EbvYCwX-ubOzU3K-CSzMrQomgiOUSJRbesUzwMQZbHxwwUtss1C4LlbJQ2yzUJvVcH4926Pj5-UQgO0JMkJva8Gv9v-o3_oKUCA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2328304690</pqid></control><display><type>article</type><title>The impact of oncogenic RAS on redox balance and implications for cancer development</title><source>MEDLINE</source><source>Nature Free</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Springer Nature OA/Free Journals</source><creator>Lim, Jonathan K. M. ; Leprivier, Gabriel</creator><creatorcontrib>Lim, Jonathan K. M. ; Leprivier, Gabriel</creatorcontrib><description>The
RAS
family of proto-oncogenes comprises
HRAS
,
KRAS
, and
NRAS
, which are among the most mutated genes in human cancers. The
RAS
family genes encode small GTPases that coordinate key signaling pathways in response to growth factors. Mutations in
RAS
result in a constitutively active form of the protein that supports cellular transformation and tumorigenesis. The mechanisms of oncogenic RAS-mediated transformation encompass uncontrolled proliferation and inhibition of cell death through overactivation of the RAF-MEK-ERK and the PI3K-AKT pathways, respectively. In addition, the control of redox balance by RAS has also been proposed to play a role in its oncogenic properties. However, the exact role of redox balance in mediating mutant RAS transformation is still under debate. Here, we present, on one hand, the involvement of pro-oxidant components in oncogenic RAS transformation, such as NADPH oxidases and mitochondrial reactive oxygen species, and how these promote transformation. On the other hand, we describe the contribution of antioxidant components to mutant RAS transformation, including Nrf2, glutathione biosynthesis and xCT, as well as the mechanisms by which antioxidant programs drive transformation. Finally, we aim to reconcile the seemingly opposite effects of oncogenic RAS on redox balance and discuss a model for the complementary role of both pro-oxidant and antioxidant pathways in mutant RAS-driven tumor progression.</description><identifier>ISSN: 2041-4889</identifier><identifier>EISSN: 2041-4889</identifier><identifier>DOI: 10.1038/s41419-019-2192-y</identifier><identifier>PMID: 31852884</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67/395 ; 631/80/86 ; Animals ; Antibodies ; Antioxidants ; Apoptosis ; Biochemistry ; Biomedical and Life Sciences ; Biosynthesis ; Cancer ; Cell Biology ; Cell Culture ; Cell cycle ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - pathology ; Gene expression ; Growth factors ; Homeostasis ; Humans ; Immunology ; Kinases ; Life Sciences ; Mutation ; Mutation - genetics ; Neoplasms - genetics ; Neoplasms - pathology ; Oncogenes - genetics ; Oxidation-Reduction ; Proteins ; ras Proteins - genetics ; Reactive Oxygen Species - metabolism ; Review ; Review Article ; Senescence ; Signal transduction ; Signal Transduction - genetics ; Tumorigenesis</subject><ispartof>Cell death & disease, 2019-12, Vol.10 (12), p.955-9, Article 955</ispartof><rights>The Author(s) 2019</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c536t-45985990581da205452059e1145d8b22db99b39607471ce8a87741fb7900de483</citedby><cites>FETCH-LOGICAL-c536t-45985990581da205452059e1145d8b22db99b39607471ce8a87741fb7900de483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920345/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920345/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31852884$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lim, Jonathan K. M.</creatorcontrib><creatorcontrib>Leprivier, Gabriel</creatorcontrib><title>The impact of oncogenic RAS on redox balance and implications for cancer development</title><title>Cell death & disease</title><addtitle>Cell Death Dis</addtitle><addtitle>Cell Death Dis</addtitle><description>The
RAS
family of proto-oncogenes comprises
HRAS
,
KRAS
, and
NRAS
, which are among the most mutated genes in human cancers. The
RAS
family genes encode small GTPases that coordinate key signaling pathways in response to growth factors. Mutations in
RAS
result in a constitutively active form of the protein that supports cellular transformation and tumorigenesis. The mechanisms of oncogenic RAS-mediated transformation encompass uncontrolled proliferation and inhibition of cell death through overactivation of the RAF-MEK-ERK and the PI3K-AKT pathways, respectively. In addition, the control of redox balance by RAS has also been proposed to play a role in its oncogenic properties. However, the exact role of redox balance in mediating mutant RAS transformation is still under debate. Here, we present, on one hand, the involvement of pro-oxidant components in oncogenic RAS transformation, such as NADPH oxidases and mitochondrial reactive oxygen species, and how these promote transformation. On the other hand, we describe the contribution of antioxidant components to mutant RAS transformation, including Nrf2, glutathione biosynthesis and xCT, as well as the mechanisms by which antioxidant programs drive transformation. Finally, we aim to reconcile the seemingly opposite effects of oncogenic RAS on redox balance and discuss a model for the complementary role of both pro-oxidant and antioxidant pathways in mutant RAS-driven tumor progression.</description><subject>631/67/395</subject><subject>631/80/86</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biosynthesis</subject><subject>Cancer</subject><subject>Cell Biology</subject><subject>Cell Culture</subject><subject>Cell cycle</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Neoplastic - pathology</subject><subject>Gene expression</subject><subject>Growth factors</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Immunology</subject><subject>Kinases</subject><subject>Life Sciences</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - pathology</subject><subject>Oncogenes - genetics</subject><subject>Oxidation-Reduction</subject><subject>Proteins</subject><subject>ras Proteins - genetics</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Review</subject><subject>Review Article</subject><subject>Senescence</subject><subject>Signal transduction</subject><subject>Signal Transduction - genetics</subject><subject>Tumorigenesis</subject><issn>2041-4889</issn><issn>2041-4889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1UU1LAzEUDKJYqf0BXiTgeTWfu8lFKMUvKAhazyGbzbZbtklNtsX-e1Naaz0YSF7CzJt5ZAC4wugWIyruIsMMywylTbAk2eYEXBDEcMaEkKdH9x4YxDhHaVGKCM_PQY9iwYkQ7AJMJjMLm8VSmw76Gnpn_NS6xsC34Xt6wWAr_wVL3WpnLNSu2pLbxuiu8S7C2gdotlCAlV3b1i8X1nWX4KzWbbSDfe2Dj8eHyeg5G78-vYyG48xwmncZ41JwKREXuNIEccbTIS3GjFeiJKQqpSypzFHBCmys0KIoGK7LQiJUWSZoH9zvdJercmErk6yDbtUyNAsdNsrrRv1FXDNTU79WuSSIMp4EbvYCwX-ubOzU3K-CSzMrQomgiOUSJRbesUzwMQZbHxwwUtss1C4LlbJQ2yzUJvVcH4926Pj5-UQgO0JMkJva8Gv9v-o3_oKUCA</recordid><startdate>20191218</startdate><enddate>20191218</enddate><creator>Lim, Jonathan K. M.</creator><creator>Leprivier, Gabriel</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20191218</creationdate><title>The impact of oncogenic RAS on redox balance and implications for cancer development</title><author>Lim, Jonathan K. M. ; Leprivier, Gabriel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c536t-45985990581da205452059e1145d8b22db99b39607471ce8a87741fb7900de483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>631/67/395</topic><topic>631/80/86</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biosynthesis</topic><topic>Cancer</topic><topic>Cell Biology</topic><topic>Cell Culture</topic><topic>Cell cycle</topic><topic>Cell Transformation, Neoplastic - genetics</topic><topic>Cell Transformation, Neoplastic - pathology</topic><topic>Gene expression</topic><topic>Growth factors</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Immunology</topic><topic>Kinases</topic><topic>Life Sciences</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - pathology</topic><topic>Oncogenes - genetics</topic><topic>Oxidation-Reduction</topic><topic>Proteins</topic><topic>ras Proteins - genetics</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Review</topic><topic>Review Article</topic><topic>Senescence</topic><topic>Signal transduction</topic><topic>Signal Transduction - genetics</topic><topic>Tumorigenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lim, Jonathan K. M.</creatorcontrib><creatorcontrib>Leprivier, Gabriel</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell death & disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lim, Jonathan K. M.</au><au>Leprivier, Gabriel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The impact of oncogenic RAS on redox balance and implications for cancer development</atitle><jtitle>Cell death & disease</jtitle><stitle>Cell Death Dis</stitle><addtitle>Cell Death Dis</addtitle><date>2019-12-18</date><risdate>2019</risdate><volume>10</volume><issue>12</issue><spage>955</spage><epage>9</epage><pages>955-9</pages><artnum>955</artnum><issn>2041-4889</issn><eissn>2041-4889</eissn><abstract>The
RAS
family of proto-oncogenes comprises
HRAS
,
KRAS
, and
NRAS
, which are among the most mutated genes in human cancers. The
RAS
family genes encode small GTPases that coordinate key signaling pathways in response to growth factors. Mutations in
RAS
result in a constitutively active form of the protein that supports cellular transformation and tumorigenesis. The mechanisms of oncogenic RAS-mediated transformation encompass uncontrolled proliferation and inhibition of cell death through overactivation of the RAF-MEK-ERK and the PI3K-AKT pathways, respectively. In addition, the control of redox balance by RAS has also been proposed to play a role in its oncogenic properties. However, the exact role of redox balance in mediating mutant RAS transformation is still under debate. Here, we present, on one hand, the involvement of pro-oxidant components in oncogenic RAS transformation, such as NADPH oxidases and mitochondrial reactive oxygen species, and how these promote transformation. On the other hand, we describe the contribution of antioxidant components to mutant RAS transformation, including Nrf2, glutathione biosynthesis and xCT, as well as the mechanisms by which antioxidant programs drive transformation. Finally, we aim to reconcile the seemingly opposite effects of oncogenic RAS on redox balance and discuss a model for the complementary role of both pro-oxidant and antioxidant pathways in mutant RAS-driven tumor progression.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31852884</pmid><doi>10.1038/s41419-019-2192-y</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/67/395 631/80/86 Animals Antibodies Antioxidants Apoptosis Biochemistry Biomedical and Life Sciences Biosynthesis Cancer Cell Biology Cell Culture Cell cycle Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - pathology Gene expression Growth factors Homeostasis Humans Immunology Kinases Life Sciences Mutation Mutation - genetics Neoplasms - genetics Neoplasms - pathology Oncogenes - genetics Oxidation-Reduction Proteins ras Proteins - genetics Reactive Oxygen Species - metabolism Review Review Article Senescence Signal transduction Signal Transduction - genetics Tumorigenesis |
| title | The impact of oncogenic RAS on redox balance and implications for cancer development |
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