Methylation of NRN1 is a novel synthetic lethal marker of PI3K‐Akt‐mTOR and ATR inhibitors in esophageal cancer
Wnt, PI3K‐Akt‐mTOR, and NF‐κB pathways were reported to be involved in DNA damage repair (DDR). DDR‐deficient cancers become critically dependent on backup DNA repair pathways. Neuritin 1 (NRN1) is reported to be involved in PI3K‐Akt‐mTOR, and its role in DDR remains unclear. Methylation‐specific PC...
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| Veröffentlicht in: | Cancer science 2021-07, Vol.112 (7), p.2870-2883 |
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| creator | Du, Wushuang Gao, Aiai Herman, James G. Wang, Lidong Zhang, Lirong Jiao, Shunchang Guo, Mingzhou |
| description | Wnt, PI3K‐Akt‐mTOR, and NF‐κB pathways were reported to be involved in DNA damage repair (DDR). DDR‐deficient cancers become critically dependent on backup DNA repair pathways. Neuritin 1 (NRN1) is reported to be involved in PI3K‐Akt‐mTOR, and its role in DDR remains unclear. Methylation‐specific PCR, siRNA, flow cytometry, esophageal cancer cell lines, and xenograft mouse models were used to examine the role of NRN1 in esophageal cancer. The expression of NRN1 is frequently repressed by promoter region methylation in human esophageal cancer cells. NRN1 was methylated in 50.4% (510/1012) of primary esophageal cancer samples. NRN1 methylation is associated significantly with age (P |
| doi_str_mv | 10.1111/cas.14917 |
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The combination of NVP‐BEZ235 and VE‐822 increased cytotoxicity in NRN1 methylated esophageal cancer cells. Methylation of NRN1 is a novel synthetic lethal marker for PI3K‐Akt‐mTOR and ATR inhibitors in human esophageal cancer.]]></description><identifier>ISSN: 1347-9032</identifier><identifier>ISSN: 1349-7006</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.14917</identifier><identifier>PMID: 33931924</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>1-Phosphatidylinositol 3-kinase ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; AKT protein ; Alcohol Drinking ; Animal models ; Animals ; Apoptosis ; Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors ; Ataxia Telangiectasia Mutated Proteins - metabolism ; ATR inhibitor ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Cancer ; Cancer therapies ; Cell cycle ; Cell Line, Tumor ; Cell migration ; Cell Movement ; Cell proliferation ; Cell Proliferation - genetics ; CHK1 protein ; Cytotoxicity ; Deoxyribonucleic acid ; DNA ; DNA Damage ; DNA damage repair ; DNA methylation ; DNA Repair ; Epigenetics ; Esophageal cancer ; Esophageal Neoplasms - genetics ; Esophageal Neoplasms - metabolism ; Esophageal Neoplasms - mortality ; Esophageal Neoplasms - pathology ; Esophageal Squamous Cell Carcinoma - genetics ; Esophageal Squamous Cell Carcinoma - metabolism ; Esophageal Squamous Cell Carcinoma - mortality ; Esophageal Squamous Cell Carcinoma - pathology ; Esophagus ; Female ; Flow cytometry ; Genomes ; GPI-Linked Proteins - genetics ; GPI-Linked Proteins - metabolism ; Heterografts ; Humans ; Male ; Methylation ; Mice ; Mice, Nude ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Neuropeptides - genetics ; Neuropeptides - metabolism ; NRN1 ; Original ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphoinositide-3 Kinase Inhibitors - therapeutic use ; PI3K signaling ; Prognosis ; Promoter Regions, Genetic ; Proto-Oncogene Proteins c-akt - antagonists & inhibitors ; Proto-Oncogene Proteins c-akt - metabolism ; Pyrazines - therapeutic use ; Pyrazoles - therapeutic use ; Signal transduction ; siRNA ; TOR protein ; TOR Serine-Threonine Kinases - antagonists & inhibitors ; TOR Serine-Threonine Kinases - metabolism ; Tumor Burden ; Tumor cell lines ; Tumors ; Wnt protein ; Xenografts</subject><ispartof>Cancer science, 2021-07, Vol.112 (7), p.2870-2883</ispartof><rights>2021 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by-nc/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-c4957-72d164a3795d1e1ccd38a1587c95e21fc19752945ebc31d86e1c449614e0dfd43</citedby><cites>FETCH-LOGICAL-c4957-72d164a3795d1e1ccd38a1587c95e21fc19752945ebc31d86e1c449614e0dfd43</cites><orcidid>0000-0002-9445-9984</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/PMC8253287/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253287/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33931924$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Du, Wushuang</creatorcontrib><creatorcontrib>Gao, Aiai</creatorcontrib><creatorcontrib>Herman, James G.</creatorcontrib><creatorcontrib>Wang, Lidong</creatorcontrib><creatorcontrib>Zhang, Lirong</creatorcontrib><creatorcontrib>Jiao, Shunchang</creatorcontrib><creatorcontrib>Guo, Mingzhou</creatorcontrib><title>Methylation of NRN1 is a novel synthetic lethal marker of PI3K‐Akt‐mTOR and ATR inhibitors in esophageal cancer</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description><![CDATA[Wnt, PI3K‐Akt‐mTOR, and NF‐κB pathways were reported to be involved in DNA damage repair (DDR). DDR‐deficient cancers become critically dependent on backup DNA repair pathways. Neuritin 1 (NRN1) is reported to be involved in PI3K‐Akt‐mTOR, and its role in DDR remains unclear. Methylation‐specific PCR, siRNA, flow cytometry, esophageal cancer cell lines, and xenograft mouse models were used to examine the role of NRN1 in esophageal cancer. The expression of NRN1 is frequently repressed by promoter region methylation in human esophageal cancer cells. NRN1 was methylated in 50.4% (510/1012) of primary esophageal cancer samples. NRN1 methylation is associated significantly with age (P < .001), tumor size (P < .01), TNM stage (P < .001), differentiation (P < .001) and alcohol consumption (P < .05). We found that NRN1 methylation is an independent prognostic factor for poor 5‐y overall survival (P < .001). NRN1 inhibits colony formation, cell proliferation, migration, and invasion, and induces apoptosis and G1/S arrest in esophageal cancer cells. NRN1 suppresses KYSE150 and KYSE30 cells xenografts growth in nude mice. PI3K signaling is reported to activate ATR signaling by targeting CHK1, the downstream component of ATR. By analyzing the synthetic efficiency of NVP‐BEZ235 (PI3K inhibitor) and VE‐822 (an ATR inhibitor), we found that the combination of NVP‐BEZ235 and VE‐822 increased cytotoxicity in NRN1 methylated esophageal cancer cells, as well as KYSE150 cell xenografts. In conclusion, NRN1 suppresses esophageal cancer growth both in vitro and in vivo by inhibiting PI3K‐Akt‐mTOR signaling. Methylation of NRN1 is a novel synthetic lethal marker for PI3K‐Akt‐mTOR and ATR inhibitors in human esophageal cancer.
The combination of NVP‐BEZ235 and VE‐822 increased cytotoxicity in NRN1 methylated esophageal cancer cells. Methylation of NRN1 is a novel synthetic lethal marker for PI3K‐Akt‐mTOR and ATR inhibitors in human esophageal cancer.]]></description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Adult</subject><subject>Age Factors</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>AKT protein</subject><subject>Alcohol Drinking</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors</subject><subject>Ataxia Telangiectasia Mutated Proteins - metabolism</subject><subject>ATR inhibitor</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - genetics</subject><subject>CHK1 protein</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>DNA damage repair</subject><subject>DNA methylation</subject><subject>DNA Repair</subject><subject>Epigenetics</subject><subject>Esophageal cancer</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Esophageal Neoplasms - metabolism</subject><subject>Esophageal Neoplasms - mortality</subject><subject>Esophageal Neoplasms - pathology</subject><subject>Esophageal Squamous Cell Carcinoma - genetics</subject><subject>Esophageal Squamous Cell Carcinoma - metabolism</subject><subject>Esophageal Squamous Cell Carcinoma - mortality</subject><subject>Esophageal Squamous Cell Carcinoma - pathology</subject><subject>Esophagus</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Genomes</subject><subject>GPI-Linked Proteins - genetics</subject><subject>GPI-Linked Proteins - metabolism</subject><subject>Heterografts</subject><subject>Humans</subject><subject>Male</subject><subject>Methylation</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Middle Aged</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Transplantation</subject><subject>Neuropeptides - genetics</subject><subject>Neuropeptides - metabolism</subject><subject>NRN1</subject><subject>Original</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphoinositide-3 Kinase Inhibitors - therapeutic use</subject><subject>PI3K signaling</subject><subject>Prognosis</subject><subject>Promoter Regions, Genetic</subject><subject>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Pyrazines - therapeutic use</subject><subject>Pyrazoles - therapeutic use</subject><subject>Signal transduction</subject><subject>siRNA</subject><subject>TOR protein</subject><subject>TOR Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><subject>Tumor Burden</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><subject>Wnt protein</subject><subject>Xenografts</subject><issn>1347-9032</issn><issn>1349-7006</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkctuEzEUhi0EohdY8ALIEhu6mNbX8XiDFEVcKkqLQlhbjudMx-3EDvakKDsegWfkSXCaUgESwovjI53v_Dq_foSeUXJMyztxNh9Toal6gPYpF7pShNQPb3tVacLZHjrI-YoQXgstHqM9zjWnmol9lD_A2G8GO_oYcOzw-eycYp-xxSHewIDzJow9jN7hoYB2wEubriFt0Y-n_P2Pb98n12Opy_nFDNvQ4sl8hn3o_cKPMeXSYshx1dtLKMvOBgfpCXrU2SHD07v_EH1-83o-fVedXbw9nU7OKie0VJViLa2F5UrLlgJ1ruWNpbJRTktgtHNUK8m0kLBwnLZNXRghdE0FkLZrBT9Er3a6q_ViCa2DMCY7mFXyxcTGROvNn5Pge3MZb0zDJGeNKgIv7wRS_LKGPJqlzw6GwQaI62yYZKSRTPG6oC_-Qq_iOoVir1C64URp_R9KKFlrJbZ3H-0ol2LOCbr7kykx28BNCdzcBl7Y5797vCd_JVyAkx3w1Q-w-beSmU4-7SR_AqSRtTU</recordid><startdate>202107</startdate><enddate>202107</enddate><creator>Du, Wushuang</creator><creator>Gao, Aiai</creator><creator>Herman, James G.</creator><creator>Wang, Lidong</creator><creator>Zhang, Lirong</creator><creator>Jiao, Shunchang</creator><creator>Guo, Mingzhou</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</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>8FE</scope><scope>8FH</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>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9445-9984</orcidid></search><sort><creationdate>202107</creationdate><title>Methylation of NRN1 is a novel synthetic lethal marker of PI3K‐Akt‐mTOR and ATR inhibitors in esophageal cancer</title><author>Du, Wushuang ; Gao, Aiai ; Herman, James G. ; Wang, Lidong ; Zhang, Lirong ; Jiao, Shunchang ; Guo, Mingzhou</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4957-72d164a3795d1e1ccd38a1587c95e21fc19752945ebc31d86e1c449614e0dfd43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Adult</topic><topic>Age Factors</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>AKT protein</topic><topic>Alcohol Drinking</topic><topic>Animal models</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors</topic><topic>Ataxia Telangiectasia Mutated Proteins - metabolism</topic><topic>ATR inhibitor</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - genetics</topic><topic>CHK1 protein</topic><topic>Cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Damage</topic><topic>DNA damage repair</topic><topic>DNA methylation</topic><topic>DNA Repair</topic><topic>Epigenetics</topic><topic>Esophageal cancer</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Esophageal Neoplasms - metabolism</topic><topic>Esophageal Neoplasms - mortality</topic><topic>Esophageal Neoplasms - pathology</topic><topic>Esophageal Squamous Cell Carcinoma - genetics</topic><topic>Esophageal Squamous Cell Carcinoma - metabolism</topic><topic>Esophageal Squamous Cell Carcinoma - mortality</topic><topic>Esophageal Squamous Cell Carcinoma - pathology</topic><topic>Esophagus</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Genomes</topic><topic>GPI-Linked Proteins - genetics</topic><topic>GPI-Linked Proteins - metabolism</topic><topic>Heterografts</topic><topic>Humans</topic><topic>Male</topic><topic>Methylation</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Middle Aged</topic><topic>Neoplasm Invasiveness</topic><topic>Neoplasm Transplantation</topic><topic>Neuropeptides - genetics</topic><topic>Neuropeptides - metabolism</topic><topic>NRN1</topic><topic>Original</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphoinositide-3 Kinase Inhibitors - therapeutic use</topic><topic>PI3K signaling</topic><topic>Prognosis</topic><topic>Promoter Regions, Genetic</topic><topic>Proto-Oncogene Proteins c-akt - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Pyrazines - therapeutic use</topic><topic>Pyrazoles - therapeutic use</topic><topic>Signal transduction</topic><topic>siRNA</topic><topic>TOR protein</topic><topic>TOR Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><topic>Tumor Burden</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><topic>Wnt protein</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Du, Wushuang</creatorcontrib><creatorcontrib>Gao, Aiai</creatorcontrib><creatorcontrib>Herman, James G.</creatorcontrib><creatorcontrib>Wang, Lidong</creatorcontrib><creatorcontrib>Zhang, Lirong</creatorcontrib><creatorcontrib>Jiao, Shunchang</creatorcontrib><creatorcontrib>Guo, Mingzhou</creatorcontrib><collection>Wiley Online Library Open Access</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 SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Du, Wushuang</au><au>Gao, Aiai</au><au>Herman, James G.</au><au>Wang, Lidong</au><au>Zhang, Lirong</au><au>Jiao, Shunchang</au><au>Guo, Mingzhou</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methylation of NRN1 is a novel synthetic lethal marker of PI3K‐Akt‐mTOR and ATR inhibitors in esophageal cancer</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2021-07</date><risdate>2021</risdate><volume>112</volume><issue>7</issue><spage>2870</spage><epage>2883</epage><pages>2870-2883</pages><issn>1347-9032</issn><issn>1349-7006</issn><eissn>1349-7006</eissn><abstract><![CDATA[Wnt, PI3K‐Akt‐mTOR, and NF‐κB pathways were reported to be involved in DNA damage repair (DDR). DDR‐deficient cancers become critically dependent on backup DNA repair pathways. Neuritin 1 (NRN1) is reported to be involved in PI3K‐Akt‐mTOR, and its role in DDR remains unclear. Methylation‐specific PCR, siRNA, flow cytometry, esophageal cancer cell lines, and xenograft mouse models were used to examine the role of NRN1 in esophageal cancer. The expression of NRN1 is frequently repressed by promoter region methylation in human esophageal cancer cells. NRN1 was methylated in 50.4% (510/1012) of primary esophageal cancer samples. NRN1 methylation is associated significantly with age (P < .001), tumor size (P < .01), TNM stage (P < .001), differentiation (P < .001) and alcohol consumption (P < .05). We found that NRN1 methylation is an independent prognostic factor for poor 5‐y overall survival (P < .001). NRN1 inhibits colony formation, cell proliferation, migration, and invasion, and induces apoptosis and G1/S arrest in esophageal cancer cells. NRN1 suppresses KYSE150 and KYSE30 cells xenografts growth in nude mice. PI3K signaling is reported to activate ATR signaling by targeting CHK1, the downstream component of ATR. By analyzing the synthetic efficiency of NVP‐BEZ235 (PI3K inhibitor) and VE‐822 (an ATR inhibitor), we found that the combination of NVP‐BEZ235 and VE‐822 increased cytotoxicity in NRN1 methylated esophageal cancer cells, as well as KYSE150 cell xenografts. In conclusion, NRN1 suppresses esophageal cancer growth both in vitro and in vivo by inhibiting PI3K‐Akt‐mTOR signaling. Methylation of NRN1 is a novel synthetic lethal marker for PI3K‐Akt‐mTOR and ATR inhibitors in human esophageal cancer.
The combination of NVP‐BEZ235 and VE‐822 increased cytotoxicity in NRN1 methylated esophageal cancer cells. Methylation of NRN1 is a novel synthetic lethal marker for PI3K‐Akt‐mTOR and ATR inhibitors in human esophageal cancer.]]></abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>33931924</pmid><doi>10.1111/cas.14917</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-9445-9984</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer science, 2021-07, Vol.112 (7), p.2870-2883 |
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| language | eng |
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| source | MEDLINE; Wiley Online Library Open Access; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; PubMed Central |
| subjects | 1-Phosphatidylinositol 3-kinase Adult Age Factors Aged Aged, 80 and over AKT protein Alcohol Drinking Animal models Animals Apoptosis Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors Ataxia Telangiectasia Mutated Proteins - metabolism ATR inhibitor Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Cancer Cancer therapies Cell cycle Cell Line, Tumor Cell migration Cell Movement Cell proliferation Cell Proliferation - genetics CHK1 protein Cytotoxicity Deoxyribonucleic acid DNA DNA Damage DNA damage repair DNA methylation DNA Repair Epigenetics Esophageal cancer Esophageal Neoplasms - genetics Esophageal Neoplasms - metabolism Esophageal Neoplasms - mortality Esophageal Neoplasms - pathology Esophageal Squamous Cell Carcinoma - genetics Esophageal Squamous Cell Carcinoma - metabolism Esophageal Squamous Cell Carcinoma - mortality Esophageal Squamous Cell Carcinoma - pathology Esophagus Female Flow cytometry Genomes GPI-Linked Proteins - genetics GPI-Linked Proteins - metabolism Heterografts Humans Male Methylation Mice Mice, Nude Middle Aged Neoplasm Invasiveness Neoplasm Transplantation Neuropeptides - genetics Neuropeptides - metabolism NRN1 Original Phosphatidylinositol 3-Kinases - metabolism Phosphoinositide-3 Kinase Inhibitors - therapeutic use PI3K signaling Prognosis Promoter Regions, Genetic Proto-Oncogene Proteins c-akt - antagonists & inhibitors Proto-Oncogene Proteins c-akt - metabolism Pyrazines - therapeutic use Pyrazoles - therapeutic use Signal transduction siRNA TOR protein TOR Serine-Threonine Kinases - antagonists & inhibitors TOR Serine-Threonine Kinases - metabolism Tumor Burden Tumor cell lines Tumors Wnt protein Xenografts |
| title | Methylation of NRN1 is a novel synthetic lethal marker of PI3K‐Akt‐mTOR and ATR inhibitors in esophageal cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T14%3A52%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Methylation%20of%20NRN1%20is%20a%20novel%20synthetic%20lethal%20marker%20of%20PI3K%E2%80%90Akt%E2%80%90mTOR%20and%20ATR%20inhibitors%20in%20esophageal%20cancer&rft.jtitle=Cancer%20science&rft.au=Du,%20Wushuang&rft.date=2021-07&rft.volume=112&rft.issue=7&rft.spage=2870&rft.epage=2883&rft.pages=2870-2883&rft.issn=1347-9032&rft.eissn=1349-7006&rft_id=info:doi/10.1111/cas.14917&rft_dat=%3Cproquest_pubme%3E2598307996%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2547569744&rft_id=info:pmid/33931924&rfr_iscdi=true |