CXCR4 Signaling Induced Epithelial-Mesenchymal Transition by PI3K/AKT and ERK Pathways in Glioblastoma
Stromal cell-derived factor 1 (SDF-1) and its receptor, CXCR4, play an important role in tumor progression. Epithelial-mesenchymal transition (EMT) process is linked to disease pathophysiology. This study aimed to investigate the roles and underlying mechanisms of SDF-1/CXCR4 axis in EMT process of...
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| Veröffentlicht in: | Molecular neurobiology 2015-12, Vol.52 (3), p.1263-1268 |
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| creator | Lv, Baoyu Yang, Xiangshan Lv, Shunzeng Wang, Lei Fan, Kaixi Shi, Ranran Wang, Fengling Song, Huishu Ma, Xiaochen Tan, Xuefen Xu, Kun Xie, Jingjing Wang, Guangmei Feng, Man Zhang, Li |
| description | Stromal cell-derived factor 1 (SDF-1) and its receptor, CXCR4, play an important role in tumor progression. Epithelial-mesenchymal transition (EMT) process is linked to disease pathophysiology. This study aimed to investigate the roles and underlying mechanisms of SDF-1/CXCR4 axis in EMT process of glioblastoma. In the present study, CXCR4 activation and inhibition in U87 were induced with exogenous SDF-1 and with CXCR4 small interfering RNA (siRNA), respectively. CXCR4 downstream signal molecules AKT, ERK, and EMT biomarkers (vementin, snail, N-cadherin, and E-cadherin) were tested using the Western blot. Our results showed that SDF-1 can induce AKT and ERK phosphorylation in a dose-dependent manner, and endogenous CXCR4 can be blocked thoroughly by CXCR4 siRNA in U87. Notably SDF-1 alone treatment can induce the upregulation of vementin, snail, and N-cadherin of U87; besides, the downregulation of E-cadherin also occurred. On the contrary, CXCR4 siRNA significantly prohibited SDF-1-induced AKT and ERK phosphorylation, at the same time, EMT biomarker changes were not observed. Function analysis revealed that CXCR4 siRNA obviously interfered with U87 cell migration and proliferation, according to wound healing assay. In conclusion, this study suggested that EMT process can be triggered by the SDF-1/CXCR4 axis in glioblastoma, and then involved in the tumor cell invasion and proliferation via activation of PI3K/AKT and ERK pathway. Our study lays a new foundation for the treatment of glioblastoma through antagonizing CXCR4. |
| doi_str_mv | 10.1007/s12035-014-8935-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1722172119</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1722172119</sourcerecordid><originalsourceid>FETCH-LOGICAL-p314t-c47141b3a6e68daff03d7724c018b17dffd7dd3c26aaee345bc9b53e303e60743</originalsourceid><addsrcrecordid>eNo1UE9LwzAcDaK4Of0AXiRHL3X5JWnTHkeZc2zimBO8lbRJt0ia1qZF-u0tOE_v8f4dHkL3QJ6AEDH3QAkLAwI8iJORDBdoCmGYBAAxvURTMqqBiHg8QTfefxFCKRBxjSY0ZDQazSkq0890z_G7OTppjTvitVN9oRVeNqY7aWukDV611644DZW0-NBK501naofzAe_WbDNfbA5YurGx3-Cd7E4_cvDYOLyyps6t9F1dyVt0VUrr9d0ZZ-jjeXlIX4Lt22qdLrZBw4B3QcEFcMiZjHQUK1mWhCkhKC8IxDkIVZZKKMUKGkmpNeNhXiR5yDQjTEdEcDZDj3-7TVt_99p3WWV8oa2VTte9z0CMFwgKkIzRh3O0zyutsqY1lWyH7P8b9gvvzWXq</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1722172119</pqid></control><display><type>article</type><title>CXCR4 Signaling Induced Epithelial-Mesenchymal Transition by PI3K/AKT and ERK Pathways in Glioblastoma</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Lv, Baoyu ; Yang, Xiangshan ; Lv, Shunzeng ; Wang, Lei ; Fan, Kaixi ; Shi, Ranran ; Wang, Fengling ; Song, Huishu ; Ma, Xiaochen ; Tan, Xuefen ; Xu, Kun ; Xie, Jingjing ; Wang, Guangmei ; Feng, Man ; Zhang, Li</creator><creatorcontrib>Lv, Baoyu ; Yang, Xiangshan ; Lv, Shunzeng ; Wang, Lei ; Fan, Kaixi ; Shi, Ranran ; Wang, Fengling ; Song, Huishu ; Ma, Xiaochen ; Tan, Xuefen ; Xu, Kun ; Xie, Jingjing ; Wang, Guangmei ; Feng, Man ; Zhang, Li</creatorcontrib><description>Stromal cell-derived factor 1 (SDF-1) and its receptor, CXCR4, play an important role in tumor progression. Epithelial-mesenchymal transition (EMT) process is linked to disease pathophysiology. This study aimed to investigate the roles and underlying mechanisms of SDF-1/CXCR4 axis in EMT process of glioblastoma. In the present study, CXCR4 activation and inhibition in U87 were induced with exogenous SDF-1 and with CXCR4 small interfering RNA (siRNA), respectively. CXCR4 downstream signal molecules AKT, ERK, and EMT biomarkers (vementin, snail, N-cadherin, and E-cadherin) were tested using the Western blot. Our results showed that SDF-1 can induce AKT and ERK phosphorylation in a dose-dependent manner, and endogenous CXCR4 can be blocked thoroughly by CXCR4 siRNA in U87. Notably SDF-1 alone treatment can induce the upregulation of vementin, snail, and N-cadherin of U87; besides, the downregulation of E-cadherin also occurred. On the contrary, CXCR4 siRNA significantly prohibited SDF-1-induced AKT and ERK phosphorylation, at the same time, EMT biomarker changes were not observed. Function analysis revealed that CXCR4 siRNA obviously interfered with U87 cell migration and proliferation, according to wound healing assay. In conclusion, this study suggested that EMT process can be triggered by the SDF-1/CXCR4 axis in glioblastoma, and then involved in the tumor cell invasion and proliferation via activation of PI3K/AKT and ERK pathway. Our study lays a new foundation for the treatment of glioblastoma through antagonizing CXCR4.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-014-8935-y</identifier><identifier>PMID: 25326893</identifier><language>eng</language><publisher>United States</publisher><subject>Antigens, CD - biosynthesis ; Antigens, CD - genetics ; Cadherins - biosynthesis ; Cadherins - genetics ; Cell Division - drug effects ; Cell Line, Tumor ; Cell Movement - drug effects ; Chemokine CXCL12 - pharmacology ; Chemokine CXCL12 - physiology ; Dose-Response Relationship, Drug ; Epithelial-Mesenchymal Transition - drug effects ; Epithelial-Mesenchymal Transition - physiology ; Glioblastoma - metabolism ; Glioblastoma - pathology ; Humans ; MAP Kinase Signaling System - drug effects ; MAP Kinase Signaling System - physiology ; Neoplasm Proteins - genetics ; Neoplasm Proteins - pharmacology ; Neoplasm Proteins - physiology ; Phosphorylation - drug effects ; Protein Processing, Post-Translational - drug effects ; Proto-Oncogene Proteins c-akt - physiology ; Receptors, CXCR4 - genetics ; Receptors, CXCR4 - physiology ; RNA Interference ; RNA, Small Interfering - genetics ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Snail Family Transcription Factors ; Transcription Factors - biosynthesis ; Transcription Factors - genetics ; Vimentin - biosynthesis ; Vimentin - genetics</subject><ispartof>Molecular neurobiology, 2015-12, Vol.52 (3), p.1263-1268</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25326893$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lv, Baoyu</creatorcontrib><creatorcontrib>Yang, Xiangshan</creatorcontrib><creatorcontrib>Lv, Shunzeng</creatorcontrib><creatorcontrib>Wang, Lei</creatorcontrib><creatorcontrib>Fan, Kaixi</creatorcontrib><creatorcontrib>Shi, Ranran</creatorcontrib><creatorcontrib>Wang, Fengling</creatorcontrib><creatorcontrib>Song, Huishu</creatorcontrib><creatorcontrib>Ma, Xiaochen</creatorcontrib><creatorcontrib>Tan, Xuefen</creatorcontrib><creatorcontrib>Xu, Kun</creatorcontrib><creatorcontrib>Xie, Jingjing</creatorcontrib><creatorcontrib>Wang, Guangmei</creatorcontrib><creatorcontrib>Feng, Man</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><title>CXCR4 Signaling Induced Epithelial-Mesenchymal Transition by PI3K/AKT and ERK Pathways in Glioblastoma</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><description>Stromal cell-derived factor 1 (SDF-1) and its receptor, CXCR4, play an important role in tumor progression. Epithelial-mesenchymal transition (EMT) process is linked to disease pathophysiology. This study aimed to investigate the roles and underlying mechanisms of SDF-1/CXCR4 axis in EMT process of glioblastoma. In the present study, CXCR4 activation and inhibition in U87 were induced with exogenous SDF-1 and with CXCR4 small interfering RNA (siRNA), respectively. CXCR4 downstream signal molecules AKT, ERK, and EMT biomarkers (vementin, snail, N-cadherin, and E-cadherin) were tested using the Western blot. Our results showed that SDF-1 can induce AKT and ERK phosphorylation in a dose-dependent manner, and endogenous CXCR4 can be blocked thoroughly by CXCR4 siRNA in U87. Notably SDF-1 alone treatment can induce the upregulation of vementin, snail, and N-cadherin of U87; besides, the downregulation of E-cadherin also occurred. On the contrary, CXCR4 siRNA significantly prohibited SDF-1-induced AKT and ERK phosphorylation, at the same time, EMT biomarker changes were not observed. Function analysis revealed that CXCR4 siRNA obviously interfered with U87 cell migration and proliferation, according to wound healing assay. In conclusion, this study suggested that EMT process can be triggered by the SDF-1/CXCR4 axis in glioblastoma, and then involved in the tumor cell invasion and proliferation via activation of PI3K/AKT and ERK pathway. Our study lays a new foundation for the treatment of glioblastoma through antagonizing CXCR4.</description><subject>Antigens, CD - biosynthesis</subject><subject>Antigens, CD - genetics</subject><subject>Cadherins - biosynthesis</subject><subject>Cadherins - genetics</subject><subject>Cell Division - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Chemokine CXCL12 - pharmacology</subject><subject>Chemokine CXCL12 - physiology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Epithelial-Mesenchymal Transition - drug effects</subject><subject>Epithelial-Mesenchymal Transition - physiology</subject><subject>Glioblastoma - metabolism</subject><subject>Glioblastoma - pathology</subject><subject>Humans</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MAP Kinase Signaling System - physiology</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - pharmacology</subject><subject>Neoplasm Proteins - physiology</subject><subject>Phosphorylation - drug effects</subject><subject>Protein Processing, Post-Translational - drug effects</subject><subject>Proto-Oncogene Proteins c-akt - physiology</subject><subject>Receptors, CXCR4 - genetics</subject><subject>Receptors, CXCR4 - physiology</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - genetics</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>Snail Family Transcription Factors</subject><subject>Transcription Factors - biosynthesis</subject><subject>Transcription Factors - genetics</subject><subject>Vimentin - biosynthesis</subject><subject>Vimentin - genetics</subject><issn>0893-7648</issn><issn>1559-1182</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1UE9LwzAcDaK4Of0AXiRHL3X5JWnTHkeZc2zimBO8lbRJt0ia1qZF-u0tOE_v8f4dHkL3QJ6AEDH3QAkLAwI8iJORDBdoCmGYBAAxvURTMqqBiHg8QTfefxFCKRBxjSY0ZDQazSkq0890z_G7OTppjTvitVN9oRVeNqY7aWukDV611644DZW0-NBK501naofzAe_WbDNfbA5YurGx3-Cd7E4_cvDYOLyyps6t9F1dyVt0VUrr9d0ZZ-jjeXlIX4Lt22qdLrZBw4B3QcEFcMiZjHQUK1mWhCkhKC8IxDkIVZZKKMUKGkmpNeNhXiR5yDQjTEdEcDZDj3-7TVt_99p3WWV8oa2VTte9z0CMFwgKkIzRh3O0zyutsqY1lWyH7P8b9gvvzWXq</recordid><startdate>20151201</startdate><enddate>20151201</enddate><creator>Lv, Baoyu</creator><creator>Yang, Xiangshan</creator><creator>Lv, Shunzeng</creator><creator>Wang, Lei</creator><creator>Fan, Kaixi</creator><creator>Shi, Ranran</creator><creator>Wang, Fengling</creator><creator>Song, Huishu</creator><creator>Ma, Xiaochen</creator><creator>Tan, Xuefen</creator><creator>Xu, Kun</creator><creator>Xie, Jingjing</creator><creator>Wang, Guangmei</creator><creator>Feng, Man</creator><creator>Zhang, Li</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TK</scope></search><sort><creationdate>20151201</creationdate><title>CXCR4 Signaling Induced Epithelial-Mesenchymal Transition by PI3K/AKT and ERK Pathways in Glioblastoma</title><author>Lv, Baoyu ; Yang, Xiangshan ; Lv, Shunzeng ; Wang, Lei ; Fan, Kaixi ; Shi, Ranran ; Wang, Fengling ; Song, Huishu ; Ma, Xiaochen ; Tan, Xuefen ; Xu, Kun ; Xie, Jingjing ; Wang, Guangmei ; Feng, Man ; Zhang, Li</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p314t-c47141b3a6e68daff03d7724c018b17dffd7dd3c26aaee345bc9b53e303e60743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Antigens, CD - biosynthesis</topic><topic>Antigens, CD - genetics</topic><topic>Cadherins - biosynthesis</topic><topic>Cadherins - genetics</topic><topic>Cell Division - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Chemokine CXCL12 - pharmacology</topic><topic>Chemokine CXCL12 - physiology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Epithelial-Mesenchymal Transition - drug effects</topic><topic>Epithelial-Mesenchymal Transition - physiology</topic><topic>Glioblastoma - metabolism</topic><topic>Glioblastoma - pathology</topic><topic>Humans</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MAP Kinase Signaling System - physiology</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - pharmacology</topic><topic>Neoplasm Proteins - physiology</topic><topic>Phosphorylation - drug effects</topic><topic>Protein Processing, Post-Translational - drug effects</topic><topic>Proto-Oncogene Proteins c-akt - physiology</topic><topic>Receptors, CXCR4 - genetics</topic><topic>Receptors, CXCR4 - physiology</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - genetics</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>Snail Family Transcription Factors</topic><topic>Transcription Factors - biosynthesis</topic><topic>Transcription Factors - genetics</topic><topic>Vimentin - biosynthesis</topic><topic>Vimentin - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lv, Baoyu</creatorcontrib><creatorcontrib>Yang, Xiangshan</creatorcontrib><creatorcontrib>Lv, Shunzeng</creatorcontrib><creatorcontrib>Wang, Lei</creatorcontrib><creatorcontrib>Fan, Kaixi</creatorcontrib><creatorcontrib>Shi, Ranran</creatorcontrib><creatorcontrib>Wang, Fengling</creatorcontrib><creatorcontrib>Song, Huishu</creatorcontrib><creatorcontrib>Ma, Xiaochen</creatorcontrib><creatorcontrib>Tan, Xuefen</creatorcontrib><creatorcontrib>Xu, Kun</creatorcontrib><creatorcontrib>Xie, Jingjing</creatorcontrib><creatorcontrib>Wang, Guangmei</creatorcontrib><creatorcontrib>Feng, Man</creatorcontrib><creatorcontrib>Zhang, Li</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Neurosciences Abstracts</collection><jtitle>Molecular neurobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lv, Baoyu</au><au>Yang, Xiangshan</au><au>Lv, Shunzeng</au><au>Wang, Lei</au><au>Fan, Kaixi</au><au>Shi, Ranran</au><au>Wang, Fengling</au><au>Song, Huishu</au><au>Ma, Xiaochen</au><au>Tan, Xuefen</au><au>Xu, Kun</au><au>Xie, Jingjing</au><au>Wang, Guangmei</au><au>Feng, Man</au><au>Zhang, Li</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CXCR4 Signaling Induced Epithelial-Mesenchymal Transition by PI3K/AKT and ERK Pathways in Glioblastoma</atitle><jtitle>Molecular neurobiology</jtitle><addtitle>Mol Neurobiol</addtitle><date>2015-12-01</date><risdate>2015</risdate><volume>52</volume><issue>3</issue><spage>1263</spage><epage>1268</epage><pages>1263-1268</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract>Stromal cell-derived factor 1 (SDF-1) and its receptor, CXCR4, play an important role in tumor progression. Epithelial-mesenchymal transition (EMT) process is linked to disease pathophysiology. This study aimed to investigate the roles and underlying mechanisms of SDF-1/CXCR4 axis in EMT process of glioblastoma. In the present study, CXCR4 activation and inhibition in U87 were induced with exogenous SDF-1 and with CXCR4 small interfering RNA (siRNA), respectively. CXCR4 downstream signal molecules AKT, ERK, and EMT biomarkers (vementin, snail, N-cadherin, and E-cadherin) were tested using the Western blot. Our results showed that SDF-1 can induce AKT and ERK phosphorylation in a dose-dependent manner, and endogenous CXCR4 can be blocked thoroughly by CXCR4 siRNA in U87. Notably SDF-1 alone treatment can induce the upregulation of vementin, snail, and N-cadherin of U87; besides, the downregulation of E-cadherin also occurred. On the contrary, CXCR4 siRNA significantly prohibited SDF-1-induced AKT and ERK phosphorylation, at the same time, EMT biomarker changes were not observed. Function analysis revealed that CXCR4 siRNA obviously interfered with U87 cell migration and proliferation, according to wound healing assay. In conclusion, this study suggested that EMT process can be triggered by the SDF-1/CXCR4 axis in glioblastoma, and then involved in the tumor cell invasion and proliferation via activation of PI3K/AKT and ERK pathway. Our study lays a new foundation for the treatment of glioblastoma through antagonizing CXCR4.</abstract><cop>United States</cop><pmid>25326893</pmid><doi>10.1007/s12035-014-8935-y</doi><tpages>6</tpages></addata></record> |
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| subjects | Antigens, CD - biosynthesis Antigens, CD - genetics Cadherins - biosynthesis Cadherins - genetics Cell Division - drug effects Cell Line, Tumor Cell Movement - drug effects Chemokine CXCL12 - pharmacology Chemokine CXCL12 - physiology Dose-Response Relationship, Drug Epithelial-Mesenchymal Transition - drug effects Epithelial-Mesenchymal Transition - physiology Glioblastoma - metabolism Glioblastoma - pathology Humans MAP Kinase Signaling System - drug effects MAP Kinase Signaling System - physiology Neoplasm Proteins - genetics Neoplasm Proteins - pharmacology Neoplasm Proteins - physiology Phosphorylation - drug effects Protein Processing, Post-Translational - drug effects Proto-Oncogene Proteins c-akt - physiology Receptors, CXCR4 - genetics Receptors, CXCR4 - physiology RNA Interference RNA, Small Interfering - genetics Signal Transduction - drug effects Signal Transduction - physiology Snail Family Transcription Factors Transcription Factors - biosynthesis Transcription Factors - genetics Vimentin - biosynthesis Vimentin - genetics |
| title | CXCR4 Signaling Induced Epithelial-Mesenchymal Transition by PI3K/AKT and ERK Pathways in Glioblastoma |
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