CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation
Receptor tyrosine kinases, such as VEGFR, PDGFR and EGFR, play important roles in renal cancer. In this study, we investigated EGFR knockout as a therapeutic approach in renal cell carcinoma (RCC). We showed that a renal cell carcinoma cell line (RC21) has higher expression of EGFR as compared to ot...
Gespeichert in:
| Veröffentlicht in: | PloS one 2020-05, Vol.15 (5), p.e0232985-e0232985 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0232985 |
|---|---|
| container_issue | 5 |
| container_start_page | e0232985 |
| container_title | PloS one |
| container_volume | 15 |
| creator | Liu, Bin Diaz Arguello, Olivia Adaly Chen, Deng Chen, Siwei Saber, Ali Haisma, Hidde J |
| description | Receptor tyrosine kinases, such as VEGFR, PDGFR and EGFR, play important roles in renal cancer. In this study, we investigated EGFR knockout as a therapeutic approach in renal cell carcinoma (RCC). We showed that a renal cell carcinoma cell line (RC21) has higher expression of EGFR as compared to other frequently used cell lines such as HEK293, A549, Hela and DLD1. Ablation of EGFR by CRISPR/Cas9 significantly restrained tumor cell growth and activated the MAPK (pERK1/2) pathway. The VEGFR and PDGFR inhibitor, sunitinib, attenuated the expression of MAPK (pERK1/2) and pAKT induced by EGFR loss and further inhibited EGFR-/- cell proliferation. We showed that loss of EGFR eventually leads to resistance to SAHA and cisplatin. Furthermore, EGFR loss induced G2/M phase arrest and resulted in an increased resistance to TNF-related apoptosis-inducing ligand (TRAIL) in renal cell carcinoma. Thus, ablation of overexpressed EGFR by CRISPR/Cas9 alone or in combination with sunitinib may be a new treatment option for renal cell carcinoma. |
| doi_str_mv | 10.1371/journal.pone.0232985 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_2403302093</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A623985362</galeid><doaj_id>oai_doaj_org_article_aa710188f7ce45218d0c2064806524af</doaj_id><sourcerecordid>A623985362</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-f0a9f4d7365c3817bb2d503087e7b0851bd6599b01b89524fc2255648101f1c83</originalsourceid><addsrcrecordid>eNqNk91qFDEUxwdRbF19A9EBQfRi13xM5uNGKEtbFwqVrXobMplkNyWTTJNMbd_AxzazOy070gsJTMLJ7_zPyZlzkuQtBAuIC_jl2vbOML3orBELgDCqSvIsOYYVRvMcAfz84HyUvPL-GgCCyzx_mRxhlEEMsuo4-bNcr66-r-etaBQLoklZrVlQ1qRWpvZWOHHXOeF9vDk9P1unyqTctrUye-i3CtvU90YFZVSderUxSirOTND30d7tfX3qREw15ULHD3NcGduytHNWKyncTup18kIy7cWbcZ8lP89Ofyy_zS8uz1fLk4s5zysU5hKwSmZNgXPCcQmLukYNARiUhShqUBJYNzmpqhrAuqwIyiRHiJA8KyGAEvISz5L3e91OW0_HInqKMoAxQKDCkVjticaya9o51TJ3Ty1TdGewbkOZC4prQRkrom5ZyoKLjCBYNoAjEKOBPMZmMmp9HaP1dSwxFyY4piei0xujtnRjb2mBUBSposCnUcDZm174QFvlhzoyI2y_yzsuAosh7w__oE-_bqQ2LD5AGWljXD6I0pMc4dhEOG6zZPEEFVcjWsVjx0kV7ROHzxOHyARxFzas956urtb_z17-mrIfD9itYDpsvdX90DJ-CmZ7kDvrvRPyscgQ0GFgHqpBh4Gh48BEt3eHP-jR6WFC8F9KQxDf</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2403302093</pqid></control><display><type>article</type><title>CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation</title><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Public Library of Science (PLoS)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Liu, Bin ; Diaz Arguello, Olivia Adaly ; Chen, Deng ; Chen, Siwei ; Saber, Ali ; Haisma, Hidde J</creator><contributor>Fujii, Hodaka</contributor><creatorcontrib>Liu, Bin ; Diaz Arguello, Olivia Adaly ; Chen, Deng ; Chen, Siwei ; Saber, Ali ; Haisma, Hidde J ; Fujii, Hodaka</creatorcontrib><description>Receptor tyrosine kinases, such as VEGFR, PDGFR and EGFR, play important roles in renal cancer. In this study, we investigated EGFR knockout as a therapeutic approach in renal cell carcinoma (RCC). We showed that a renal cell carcinoma cell line (RC21) has higher expression of EGFR as compared to other frequently used cell lines such as HEK293, A549, Hela and DLD1. Ablation of EGFR by CRISPR/Cas9 significantly restrained tumor cell growth and activated the MAPK (pERK1/2) pathway. The VEGFR and PDGFR inhibitor, sunitinib, attenuated the expression of MAPK (pERK1/2) and pAKT induced by EGFR loss and further inhibited EGFR-/- cell proliferation. We showed that loss of EGFR eventually leads to resistance to SAHA and cisplatin. Furthermore, EGFR loss induced G2/M phase arrest and resulted in an increased resistance to TNF-related apoptosis-inducing ligand (TRAIL) in renal cell carcinoma. Thus, ablation of overexpressed EGFR by CRISPR/Cas9 alone or in combination with sunitinib may be a new treatment option for renal cell carcinoma.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0232985</identifier><identifier>PMID: 32413049</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Ablation ; Antibodies ; Apoptosis ; Biology ; Biology and Life Sciences ; Biotechnology ; Cancer ; Cancer therapies ; Carcinoma, Renal cell ; Care and treatment ; Cell proliferation ; Cervical cancer ; Cisplatin ; Cloning ; CRISPR ; Deoxyribonucleic acid ; Development and progression ; DNA ; Epidermal growth factor ; Epidermal growth factor receptors ; Genetic aspects ; Hypertension ; Inhibitor drugs ; Kidney cancer ; Kinases ; MAP kinase ; Medical prognosis ; Medicine and Health Sciences ; Penicillin ; Pharmaceuticals ; Pharmacy ; Plasmids ; Proteins ; Renal cell carcinoma ; Research and Analysis Methods ; Targeted cancer therapy ; TRAIL protein ; Tumor necrosis factor ; Tyrosine ; Vascular endothelial growth factor receptors</subject><ispartof>PloS one, 2020-05, Vol.15 (5), p.e0232985-e0232985</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Liu et al 2020 Liu et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-f0a9f4d7365c3817bb2d503087e7b0851bd6599b01b89524fc2255648101f1c83</citedby><cites>FETCH-LOGICAL-c692t-f0a9f4d7365c3817bb2d503087e7b0851bd6599b01b89524fc2255648101f1c83</cites><orcidid>0000-0002-3168-8456</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/PMC7228069/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228069/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32413049$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Fujii, Hodaka</contributor><creatorcontrib>Liu, Bin</creatorcontrib><creatorcontrib>Diaz Arguello, Olivia Adaly</creatorcontrib><creatorcontrib>Chen, Deng</creatorcontrib><creatorcontrib>Chen, Siwei</creatorcontrib><creatorcontrib>Saber, Ali</creatorcontrib><creatorcontrib>Haisma, Hidde J</creatorcontrib><title>CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Receptor tyrosine kinases, such as VEGFR, PDGFR and EGFR, play important roles in renal cancer. In this study, we investigated EGFR knockout as a therapeutic approach in renal cell carcinoma (RCC). We showed that a renal cell carcinoma cell line (RC21) has higher expression of EGFR as compared to other frequently used cell lines such as HEK293, A549, Hela and DLD1. Ablation of EGFR by CRISPR/Cas9 significantly restrained tumor cell growth and activated the MAPK (pERK1/2) pathway. The VEGFR and PDGFR inhibitor, sunitinib, attenuated the expression of MAPK (pERK1/2) and pAKT induced by EGFR loss and further inhibited EGFR-/- cell proliferation. We showed that loss of EGFR eventually leads to resistance to SAHA and cisplatin. Furthermore, EGFR loss induced G2/M phase arrest and resulted in an increased resistance to TNF-related apoptosis-inducing ligand (TRAIL) in renal cell carcinoma. Thus, ablation of overexpressed EGFR by CRISPR/Cas9 alone or in combination with sunitinib may be a new treatment option for renal cell carcinoma.</description><subject>Ablation</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Biology</subject><subject>Biology and Life Sciences</subject><subject>Biotechnology</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Carcinoma, Renal cell</subject><subject>Care and treatment</subject><subject>Cell proliferation</subject><subject>Cervical cancer</subject><subject>Cisplatin</subject><subject>Cloning</subject><subject>CRISPR</subject><subject>Deoxyribonucleic acid</subject><subject>Development and progression</subject><subject>DNA</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptors</subject><subject>Genetic aspects</subject><subject>Hypertension</subject><subject>Inhibitor drugs</subject><subject>Kidney cancer</subject><subject>Kinases</subject><subject>MAP kinase</subject><subject>Medical prognosis</subject><subject>Medicine and Health Sciences</subject><subject>Penicillin</subject><subject>Pharmaceuticals</subject><subject>Pharmacy</subject><subject>Plasmids</subject><subject>Proteins</subject><subject>Renal cell carcinoma</subject><subject>Research and Analysis Methods</subject><subject>Targeted cancer therapy</subject><subject>TRAIL protein</subject><subject>Tumor necrosis factor</subject><subject>Tyrosine</subject><subject>Vascular endothelial growth factor receptors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk91qFDEUxwdRbF19A9EBQfRi13xM5uNGKEtbFwqVrXobMplkNyWTTJNMbd_AxzazOy070gsJTMLJ7_zPyZlzkuQtBAuIC_jl2vbOML3orBELgDCqSvIsOYYVRvMcAfz84HyUvPL-GgCCyzx_mRxhlEEMsuo4-bNcr66-r-etaBQLoklZrVlQ1qRWpvZWOHHXOeF9vDk9P1unyqTctrUye-i3CtvU90YFZVSderUxSirOTND30d7tfX3qREw15ULHD3NcGduytHNWKyncTup18kIy7cWbcZ8lP89Ofyy_zS8uz1fLk4s5zysU5hKwSmZNgXPCcQmLukYNARiUhShqUBJYNzmpqhrAuqwIyiRHiJA8KyGAEvISz5L3e91OW0_HInqKMoAxQKDCkVjticaya9o51TJ3Ty1TdGewbkOZC4prQRkrom5ZyoKLjCBYNoAjEKOBPMZmMmp9HaP1dSwxFyY4piei0xujtnRjb2mBUBSposCnUcDZm174QFvlhzoyI2y_yzsuAosh7w__oE-_bqQ2LD5AGWljXD6I0pMc4dhEOG6zZPEEFVcjWsVjx0kV7ROHzxOHyARxFzas956urtb_z17-mrIfD9itYDpsvdX90DJ-CmZ7kDvrvRPyscgQ0GFgHqpBh4Gh48BEt3eHP-jR6WFC8F9KQxDf</recordid><startdate>20200515</startdate><enddate>20200515</enddate><creator>Liu, Bin</creator><creator>Diaz Arguello, Olivia Adaly</creator><creator>Chen, Deng</creator><creator>Chen, Siwei</creator><creator>Saber, Ali</creator><creator>Haisma, Hidde J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3168-8456</orcidid></search><sort><creationdate>20200515</creationdate><title>CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation</title><author>Liu, Bin ; Diaz Arguello, Olivia Adaly ; Chen, Deng ; Chen, Siwei ; Saber, Ali ; Haisma, Hidde J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-f0a9f4d7365c3817bb2d503087e7b0851bd6599b01b89524fc2255648101f1c83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Ablation</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Biology</topic><topic>Biology and Life Sciences</topic><topic>Biotechnology</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Carcinoma, Renal cell</topic><topic>Care and treatment</topic><topic>Cell proliferation</topic><topic>Cervical cancer</topic><topic>Cisplatin</topic><topic>Cloning</topic><topic>CRISPR</topic><topic>Deoxyribonucleic acid</topic><topic>Development and progression</topic><topic>DNA</topic><topic>Epidermal growth factor</topic><topic>Epidermal growth factor receptors</topic><topic>Genetic aspects</topic><topic>Hypertension</topic><topic>Inhibitor drugs</topic><topic>Kidney cancer</topic><topic>Kinases</topic><topic>MAP kinase</topic><topic>Medical prognosis</topic><topic>Medicine and Health Sciences</topic><topic>Penicillin</topic><topic>Pharmaceuticals</topic><topic>Pharmacy</topic><topic>Plasmids</topic><topic>Proteins</topic><topic>Renal cell carcinoma</topic><topic>Research and Analysis Methods</topic><topic>Targeted cancer therapy</topic><topic>TRAIL protein</topic><topic>Tumor necrosis factor</topic><topic>Tyrosine</topic><topic>Vascular endothelial growth factor receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Bin</creatorcontrib><creatorcontrib>Diaz Arguello, Olivia Adaly</creatorcontrib><creatorcontrib>Chen, Deng</creatorcontrib><creatorcontrib>Chen, Siwei</creatorcontrib><creatorcontrib>Saber, Ali</creatorcontrib><creatorcontrib>Haisma, Hidde J</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Bin</au><au>Diaz Arguello, Olivia Adaly</au><au>Chen, Deng</au><au>Chen, Siwei</au><au>Saber, Ali</au><au>Haisma, Hidde J</au><au>Fujii, Hodaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-05-15</date><risdate>2020</risdate><volume>15</volume><issue>5</issue><spage>e0232985</spage><epage>e0232985</epage><pages>e0232985-e0232985</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Receptor tyrosine kinases, such as VEGFR, PDGFR and EGFR, play important roles in renal cancer. In this study, we investigated EGFR knockout as a therapeutic approach in renal cell carcinoma (RCC). We showed that a renal cell carcinoma cell line (RC21) has higher expression of EGFR as compared to other frequently used cell lines such as HEK293, A549, Hela and DLD1. Ablation of EGFR by CRISPR/Cas9 significantly restrained tumor cell growth and activated the MAPK (pERK1/2) pathway. The VEGFR and PDGFR inhibitor, sunitinib, attenuated the expression of MAPK (pERK1/2) and pAKT induced by EGFR loss and further inhibited EGFR-/- cell proliferation. We showed that loss of EGFR eventually leads to resistance to SAHA and cisplatin. Furthermore, EGFR loss induced G2/M phase arrest and resulted in an increased resistance to TNF-related apoptosis-inducing ligand (TRAIL) in renal cell carcinoma. Thus, ablation of overexpressed EGFR by CRISPR/Cas9 alone or in combination with sunitinib may be a new treatment option for renal cell carcinoma.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32413049</pmid><doi>10.1371/journal.pone.0232985</doi><tpages>e0232985</tpages><orcidid>https://orcid.org/0000-0002-3168-8456</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-05, Vol.15 (5), p.e0232985-e0232985 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2403302093 |
| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Ablation Antibodies Apoptosis Biology Biology and Life Sciences Biotechnology Cancer Cancer therapies Carcinoma, Renal cell Care and treatment Cell proliferation Cervical cancer Cisplatin Cloning CRISPR Deoxyribonucleic acid Development and progression DNA Epidermal growth factor Epidermal growth factor receptors Genetic aspects Hypertension Inhibitor drugs Kidney cancer Kinases MAP kinase Medical prognosis Medicine and Health Sciences Penicillin Pharmaceuticals Pharmacy Plasmids Proteins Renal cell carcinoma Research and Analysis Methods Targeted cancer therapy TRAIL protein Tumor necrosis factor Tyrosine Vascular endothelial growth factor receptors |
| title | CRISPR-mediated ablation of overexpressed EGFR in combination with sunitinib significantly suppresses renal cell carcinoma proliferation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T03%3A29%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=CRISPR-mediated%20ablation%20of%20overexpressed%20EGFR%20in%20combination%20with%20sunitinib%20significantly%20suppresses%20renal%20cell%20carcinoma%20proliferation&rft.jtitle=PloS%20one&rft.au=Liu,%20Bin&rft.date=2020-05-15&rft.volume=15&rft.issue=5&rft.spage=e0232985&rft.epage=e0232985&rft.pages=e0232985-e0232985&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0232985&rft_dat=%3Cgale_plos_%3EA623985362%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2403302093&rft_id=info:pmid/32413049&rft_galeid=A623985362&rft_doaj_id=oai_doaj_org_article_aa710188f7ce45218d0c2064806524af&rfr_iscdi=true |