Osteopontin improves sensitivity to tyrosine kinase inhibitor in lung adenocarcinoma in vitro by promoting epidermal growth factor receptor phosphorylation
Purpose Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) improve the prognosis of lung adenocarcinoma (LUAD). However, the factors affecting its clinical efficacy remain unclear. This study aimed to determine the correlation between Osteopontin (OPN) and EGFR, and...
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| Veröffentlicht in: | Journal of cancer research and clinical oncology 2021-11, Vol.147 (11), p.3245-3254 |
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| container_issue | 11 |
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| container_title | Journal of cancer research and clinical oncology |
| container_volume | 147 |
| creator | Wang, Yu-Jin Wang, Qing-Wen Yu, Dong-Hu Song, Cong-Kuan Guo, Zi-Xin Liu, Xiao-Ping Chen, Chen Yao, Jie Wang, Ai-Fen Hu, Wei-Dong |
| description | Purpose
Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) improve the prognosis of lung adenocarcinoma (LUAD). However, the factors affecting its clinical efficacy remain unclear. This study aimed to determine the correlation between Osteopontin (OPN) and EGFR, and explore the inhibitory effect of first-generation TKI gefitinib on LUAD cells.
Methods
The correlation between OPN and EGFR was determined through bioinformatics technology, and the clinical information as well as samples of related patients were collected to verify the relationship between them. Using three different NSCLC cell lines A549, H1299 and PC9, we studied the effects of OPN expression and EGFR phosphorylation on the first-generation TKI’s efficacy in vitro.
Results
Our data revealed that OPN staining positively linked to a more advanced clinical stage. Compared with the control group, LUAD cells with elevated OPN levels are more sensitive to the growth inhibitory effect of TKI. Knocking down of OPN decreased the response of cells to gefitinib. Besides, OPN also upregulated the phosphorylation of EGFR, thereby affecting the effect of TKI.
Conclusion
OPN enhanced the sensitivity of LUAD cells to gefitinib by promoting EGFR phosphorylation. OPN may be a potential target for evaluating TKI efficacy and a potential target for molecular therapy. |
| doi_str_mv | 10.1007/s00432-021-03731-2 |
| format | Article |
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Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) improve the prognosis of lung adenocarcinoma (LUAD). However, the factors affecting its clinical efficacy remain unclear. This study aimed to determine the correlation between Osteopontin (OPN) and EGFR, and explore the inhibitory effect of first-generation TKI gefitinib on LUAD cells.
Methods
The correlation between OPN and EGFR was determined through bioinformatics technology, and the clinical information as well as samples of related patients were collected to verify the relationship between them. Using three different NSCLC cell lines A549, H1299 and PC9, we studied the effects of OPN expression and EGFR phosphorylation on the first-generation TKI’s efficacy in vitro.
Results
Our data revealed that OPN staining positively linked to a more advanced clinical stage. Compared with the control group, LUAD cells with elevated OPN levels are more sensitive to the growth inhibitory effect of TKI. Knocking down of OPN decreased the response of cells to gefitinib. Besides, OPN also upregulated the phosphorylation of EGFR, thereby affecting the effect of TKI.
Conclusion
OPN enhanced the sensitivity of LUAD cells to gefitinib by promoting EGFR phosphorylation. OPN may be a potential target for evaluating TKI efficacy and a potential target for molecular therapy.</description><identifier>ISSN: 0171-5216</identifier><identifier>EISSN: 1432-1335</identifier><identifier>DOI: 10.1007/s00432-021-03731-2</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adenocarcinoma ; Bioinformatics ; Cancer ; Cancer Research ; Enzyme inhibitors ; Epidermal growth factor ; Epidermal growth factor receptors ; Gefitinib ; Hematology ; Internal Medicine ; Lung cancer ; Medicine ; Medicine & Public Health ; Non-small cell lung carcinoma ; Oncology ; Original Article – Cancer Research ; Osteopontin ; Phosphorylation ; Tyrosine kinase inhibitors</subject><ispartof>Journal of cancer research and clinical oncology, 2021-11, Vol.147 (11), p.3245-3254</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021</rights><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c352t-5a16f6531873cabd166524b57ea36733f2d0b14381a9ed27049529f2b2ada3f73</citedby><cites>FETCH-LOGICAL-c352t-5a16f6531873cabd166524b57ea36733f2d0b14381a9ed27049529f2b2ada3f73</cites><orcidid>0000-0003-3646-8572</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00432-021-03731-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00432-021-03731-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids></links><search><creatorcontrib>Wang, Yu-Jin</creatorcontrib><creatorcontrib>Wang, Qing-Wen</creatorcontrib><creatorcontrib>Yu, Dong-Hu</creatorcontrib><creatorcontrib>Song, Cong-Kuan</creatorcontrib><creatorcontrib>Guo, Zi-Xin</creatorcontrib><creatorcontrib>Liu, Xiao-Ping</creatorcontrib><creatorcontrib>Chen, Chen</creatorcontrib><creatorcontrib>Yao, Jie</creatorcontrib><creatorcontrib>Wang, Ai-Fen</creatorcontrib><creatorcontrib>Hu, Wei-Dong</creatorcontrib><title>Osteopontin improves sensitivity to tyrosine kinase inhibitor in lung adenocarcinoma in vitro by promoting epidermal growth factor receptor phosphorylation</title><title>Journal of cancer research and clinical oncology</title><addtitle>J Cancer Res Clin Oncol</addtitle><description>Purpose
Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) improve the prognosis of lung adenocarcinoma (LUAD). However, the factors affecting its clinical efficacy remain unclear. This study aimed to determine the correlation between Osteopontin (OPN) and EGFR, and explore the inhibitory effect of first-generation TKI gefitinib on LUAD cells.
Methods
The correlation between OPN and EGFR was determined through bioinformatics technology, and the clinical information as well as samples of related patients were collected to verify the relationship between them. Using three different NSCLC cell lines A549, H1299 and PC9, we studied the effects of OPN expression and EGFR phosphorylation on the first-generation TKI’s efficacy in vitro.
Results
Our data revealed that OPN staining positively linked to a more advanced clinical stage. Compared with the control group, LUAD cells with elevated OPN levels are more sensitive to the growth inhibitory effect of TKI. Knocking down of OPN decreased the response of cells to gefitinib. Besides, OPN also upregulated the phosphorylation of EGFR, thereby affecting the effect of TKI.
Conclusion
OPN enhanced the sensitivity of LUAD cells to gefitinib by promoting EGFR phosphorylation. OPN may be a potential target for evaluating TKI efficacy and a potential target for molecular therapy.</description><subject>Adenocarcinoma</subject><subject>Bioinformatics</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Enzyme inhibitors</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptors</subject><subject>Gefitinib</subject><subject>Hematology</subject><subject>Internal Medicine</subject><subject>Lung cancer</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Non-small cell lung carcinoma</subject><subject>Oncology</subject><subject>Original Article – Cancer Research</subject><subject>Osteopontin</subject><subject>Phosphorylation</subject><subject>Tyrosine kinase inhibitors</subject><issn>0171-5216</issn><issn>1432-1335</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kc1KLDEQhYMoOP68gKvA3bhpTSqTzvRSRO8VBDe6Dunu6plod9I3ySj9LL6saUcQXLgIqSrO-SjqEHLG2QVnTF1GxpYCCga8YEIJXsAeWfB5xIWQ-2TBuOKFBF4ekqMYn1nupYIFeX-ICf3oXbKO2mEM_hUjjeiiTfbVpokmT9MUfLQO6Yt1JiK1bmNrm3zIFe23bk1Ni843JjTW-cHM4-wNntYTzcjBZ_qa4mhbDIPp6Tr4t7ShnWlmSMAGx7kYNz7mF6beJOvdCTnoTB_x9Os_Jk-3N4_X_4r7h79311f3RSMkpEIaXnalFHylRGPqlpelhGUtFRpRKiE6aFmdb7HipsIWFFtWEqoOajCtEZ0Sx-R8x82r_t9iTHqwscG-Nw79NmqQkgOrVssqS__8kD77bXB5u6xSquIK1AyEnarJd4sBOz0GO5gwac70nJfe5aVzXvozLw3ZJHammMVujeEb_YvrA3kJnJQ</recordid><startdate>20211101</startdate><enddate>20211101</enddate><creator>Wang, Yu-Jin</creator><creator>Wang, Qing-Wen</creator><creator>Yu, Dong-Hu</creator><creator>Song, Cong-Kuan</creator><creator>Guo, Zi-Xin</creator><creator>Liu, Xiao-Ping</creator><creator>Chen, Chen</creator><creator>Yao, Jie</creator><creator>Wang, Ai-Fen</creator><creator>Hu, Wei-Dong</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3646-8572</orcidid></search><sort><creationdate>20211101</creationdate><title>Osteopontin improves sensitivity to tyrosine kinase inhibitor in lung adenocarcinoma in vitro by promoting epidermal growth factor receptor phosphorylation</title><author>Wang, Yu-Jin ; Wang, Qing-Wen ; Yu, Dong-Hu ; Song, Cong-Kuan ; Guo, Zi-Xin ; Liu, Xiao-Ping ; Chen, Chen ; Yao, Jie ; Wang, Ai-Fen ; Hu, Wei-Dong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c352t-5a16f6531873cabd166524b57ea36733f2d0b14381a9ed27049529f2b2ada3f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenocarcinoma</topic><topic>Bioinformatics</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Enzyme inhibitors</topic><topic>Epidermal growth factor</topic><topic>Epidermal growth factor receptors</topic><topic>Gefitinib</topic><topic>Hematology</topic><topic>Internal Medicine</topic><topic>Lung cancer</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Non-small cell lung carcinoma</topic><topic>Oncology</topic><topic>Original Article – Cancer Research</topic><topic>Osteopontin</topic><topic>Phosphorylation</topic><topic>Tyrosine kinase inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yu-Jin</creatorcontrib><creatorcontrib>Wang, Qing-Wen</creatorcontrib><creatorcontrib>Yu, Dong-Hu</creatorcontrib><creatorcontrib>Song, Cong-Kuan</creatorcontrib><creatorcontrib>Guo, Zi-Xin</creatorcontrib><creatorcontrib>Liu, Xiao-Ping</creatorcontrib><creatorcontrib>Chen, Chen</creatorcontrib><creatorcontrib>Yao, Jie</creatorcontrib><creatorcontrib>Wang, Ai-Fen</creatorcontrib><creatorcontrib>Hu, Wei-Dong</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</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>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</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>MEDLINE - Academic</collection><jtitle>Journal of cancer research and clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yu-Jin</au><au>Wang, Qing-Wen</au><au>Yu, Dong-Hu</au><au>Song, Cong-Kuan</au><au>Guo, Zi-Xin</au><au>Liu, Xiao-Ping</au><au>Chen, Chen</au><au>Yao, Jie</au><au>Wang, Ai-Fen</au><au>Hu, Wei-Dong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Osteopontin improves sensitivity to tyrosine kinase inhibitor in lung adenocarcinoma in vitro by promoting epidermal growth factor receptor phosphorylation</atitle><jtitle>Journal of cancer research and clinical oncology</jtitle><stitle>J Cancer Res Clin Oncol</stitle><date>2021-11-01</date><risdate>2021</risdate><volume>147</volume><issue>11</issue><spage>3245</spage><epage>3254</epage><pages>3245-3254</pages><issn>0171-5216</issn><eissn>1432-1335</eissn><abstract>Purpose
Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) improve the prognosis of lung adenocarcinoma (LUAD). However, the factors affecting its clinical efficacy remain unclear. This study aimed to determine the correlation between Osteopontin (OPN) and EGFR, and explore the inhibitory effect of first-generation TKI gefitinib on LUAD cells.
Methods
The correlation between OPN and EGFR was determined through bioinformatics technology, and the clinical information as well as samples of related patients were collected to verify the relationship between them. Using three different NSCLC cell lines A549, H1299 and PC9, we studied the effects of OPN expression and EGFR phosphorylation on the first-generation TKI’s efficacy in vitro.
Results
Our data revealed that OPN staining positively linked to a more advanced clinical stage. Compared with the control group, LUAD cells with elevated OPN levels are more sensitive to the growth inhibitory effect of TKI. Knocking down of OPN decreased the response of cells to gefitinib. Besides, OPN also upregulated the phosphorylation of EGFR, thereby affecting the effect of TKI.
Conclusion
OPN enhanced the sensitivity of LUAD cells to gefitinib by promoting EGFR phosphorylation. OPN may be a potential target for evaluating TKI efficacy and a potential target for molecular therapy.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><doi>10.1007/s00432-021-03731-2</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-3646-8572</orcidid></addata></record> |
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| subjects | Adenocarcinoma Bioinformatics Cancer Cancer Research Enzyme inhibitors Epidermal growth factor Epidermal growth factor receptors Gefitinib Hematology Internal Medicine Lung cancer Medicine Medicine & Public Health Non-small cell lung carcinoma Oncology Original Article – Cancer Research Osteopontin Phosphorylation Tyrosine kinase inhibitors |
| title | Osteopontin improves sensitivity to tyrosine kinase inhibitor in lung adenocarcinoma in vitro by promoting epidermal growth factor receptor phosphorylation |
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