Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma
Sphingosine kinase 1 (SPHK1) has been shown to be involved in the progression of various types of human cancers. We previously demonstrated that SPHK1 is overexpressed and associated with clinical stage, locoregional recurrence, distant metastasis and poor prognosis in nasopharyngeal carcinoma (NPC)...
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| Veröffentlicht in: | Oncotarget 2016-12, Vol.7 (49), p.80586-80598 |
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| creator | Li, Wenhua Li, Jian Wang, Yunchao Zhang, Keqian Li, Ni Tian, Zhiqiang Ni, Bing Wang, Huaizhi Ruan, Zhihua |
| description | Sphingosine kinase 1 (SPHK1) has been shown to be involved in the progression of various types of human cancers. We previously demonstrated that SPHK1 is overexpressed and associated with clinical stage, locoregional recurrence, distant metastasis and poor prognosis in nasopharyngeal carcinoma (NPC). However, the biological roles involving SPHK1 and its potential usefulness as a therapeutic target in NPC remain unknown. In this study, Blocking SPHK1 using siRNA or FTY720 (a SPHK1 inhibitor) significantly reduced proliferation and migration and increased cell cycle arrest and apoptosis in NPC cells. FTY720 also decreased SPHK1 activity, and overexpressing SPHK1 abrogated the FTY720-induced effects on cell viability. In addition, FTY720 sensitized NPC cells to radiotherapy by inhibiting SPHK1 activity in vitro and in vivo. Furthermore, high SPHK1 expression was associated with increased Ki-67 and p-Akt and decreased caspase-3 expression in human NPC specimens. These data suggest that SPHK1 might be a potential therapeutic target for NPC. |
| doi_str_mv | 10.18632/oncotarget.13014 |
| format | Article |
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We previously demonstrated that SPHK1 is overexpressed and associated with clinical stage, locoregional recurrence, distant metastasis and poor prognosis in nasopharyngeal carcinoma (NPC). However, the biological roles involving SPHK1 and its potential usefulness as a therapeutic target in NPC remain unknown. In this study, Blocking SPHK1 using siRNA or FTY720 (a SPHK1 inhibitor) significantly reduced proliferation and migration and increased cell cycle arrest and apoptosis in NPC cells. FTY720 also decreased SPHK1 activity, and overexpressing SPHK1 abrogated the FTY720-induced effects on cell viability. In addition, FTY720 sensitized NPC cells to radiotherapy by inhibiting SPHK1 activity in vitro and in vivo. Furthermore, high SPHK1 expression was associated with increased Ki-67 and p-Akt and decreased caspase-3 expression in human NPC specimens. These data suggest that SPHK1 might be a potential therapeutic target for NPC.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.13014</identifier><identifier>PMID: 27811359</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Animals ; Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; Apoptosis - radiation effects ; Carcinoma - enzymology ; Carcinoma - genetics ; Carcinoma - pathology ; Carcinoma - therapy ; Caspase 3 - metabolism ; Cell Cycle Checkpoints - drug effects ; Cell Cycle Checkpoints - radiation effects ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Cell Proliferation - radiation effects ; Chemoradiotherapy ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Radiation ; Female ; Fingolimod Hydrochloride - pharmacology ; Humans ; Ki-67 Antigen - metabolism ; Mice, Inbred BALB C ; Mice, Nude ; Molecular Targeted Therapy ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms - enzymology ; Nasopharyngeal Neoplasms - genetics ; Nasopharyngeal Neoplasms - pathology ; Nasopharyngeal Neoplasms - therapy ; Phosphorylation ; Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors ; Phosphotransferases (Alcohol Group Acceptor) - genetics ; Phosphotransferases (Alcohol Group Acceptor) - metabolism ; Protein Kinase Inhibitors - pharmacology ; Proto-Oncogene Proteins c-akt - metabolism ; Research Paper ; RNA Interference ; Signal Transduction - drug effects ; Signal Transduction - radiation effects ; Time Factors ; Transfection ; Xenograft Model Antitumor Assays</subject><ispartof>Oncotarget, 2016-12, Vol.7 (49), p.80586-80598</ispartof><rights>Copyright: © 2016 Li et al. 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-625b72937b89370be9d66fa0b7c52d5495ea0fe8cb47b71d3753c145d93f5f423</citedby><cites>FETCH-LOGICAL-c356t-625b72937b89370be9d66fa0b7c52d5495ea0fe8cb47b71d3753c145d93f5f423</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/PMC5348343/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5348343/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27811359$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Wenhua</creatorcontrib><creatorcontrib>Li, Jian</creatorcontrib><creatorcontrib>Wang, Yunchao</creatorcontrib><creatorcontrib>Zhang, Keqian</creatorcontrib><creatorcontrib>Li, Ni</creatorcontrib><creatorcontrib>Tian, Zhiqiang</creatorcontrib><creatorcontrib>Ni, Bing</creatorcontrib><creatorcontrib>Wang, Huaizhi</creatorcontrib><creatorcontrib>Ruan, Zhihua</creatorcontrib><title>Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Sphingosine kinase 1 (SPHK1) has been shown to be involved in the progression of various types of human cancers. We previously demonstrated that SPHK1 is overexpressed and associated with clinical stage, locoregional recurrence, distant metastasis and poor prognosis in nasopharyngeal carcinoma (NPC). However, the biological roles involving SPHK1 and its potential usefulness as a therapeutic target in NPC remain unknown. In this study, Blocking SPHK1 using siRNA or FTY720 (a SPHK1 inhibitor) significantly reduced proliferation and migration and increased cell cycle arrest and apoptosis in NPC cells. FTY720 also decreased SPHK1 activity, and overexpressing SPHK1 abrogated the FTY720-induced effects on cell viability. In addition, FTY720 sensitized NPC cells to radiotherapy by inhibiting SPHK1 activity in vitro and in vivo. Furthermore, high SPHK1 expression was associated with increased Ki-67 and p-Akt and decreased caspase-3 expression in human NPC specimens. These data suggest that SPHK1 might be a potential therapeutic target for NPC.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - radiation effects</subject><subject>Carcinoma - enzymology</subject><subject>Carcinoma - genetics</subject><subject>Carcinoma - pathology</subject><subject>Carcinoma - therapy</subject><subject>Caspase 3 - metabolism</subject><subject>Cell Cycle Checkpoints - drug effects</subject><subject>Cell Cycle Checkpoints - radiation effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Proliferation - radiation effects</subject><subject>Chemoradiotherapy</subject><subject>Dose-Response Relationship, Drug</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Female</subject><subject>Fingolimod Hydrochloride - pharmacology</subject><subject>Humans</subject><subject>Ki-67 Antigen - metabolism</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Molecular Targeted Therapy</subject><subject>Nasopharyngeal Carcinoma</subject><subject>Nasopharyngeal Neoplasms - enzymology</subject><subject>Nasopharyngeal Neoplasms - genetics</subject><subject>Nasopharyngeal Neoplasms - pathology</subject><subject>Nasopharyngeal Neoplasms - therapy</subject><subject>Phosphorylation</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - genetics</subject><subject>Phosphotransferases (Alcohol Group Acceptor) - metabolism</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Research Paper</subject><subject>RNA Interference</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - radiation effects</subject><subject>Time Factors</subject><subject>Transfection</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1LAzEQDaLYUv0BXiRHL61JJtnsXgQpfkHBg3oO2Wy2jW6TNdkK_ntD60edw8zAvHnzmIfQGSUzWhbALoM3YdBxaYcZBUL5ARrTildTJgQc7vUjdJrSK8khuCxZdYxGTJaUgqjG6OmpXzm_DMl5i9-c18liil3CGvdhsH5wusPDykbd283gDN5dxG2IOINDv9Lx0y9tRhkdjfNhrU_QUau7ZE-_6wS93N48z--ni8e7h_n1YmpAFMO0YKKWrAJZlzmR2lZNUbSa1NII1gheCatJa0tTc1lL2oAUYCgXTQWtaDmDCbra8fabem0bk9VG3ak-unUWpYJ26v_Eu5Vahg8lgJfAIRNcfBPE8L6xaVBrl4ztOu1t2CRFSygkEGAkQ-kOamJIKdr29wwlauuH-vNDbf3IO-f7-n43fr4PX_C_iwI</recordid><startdate>20161206</startdate><enddate>20161206</enddate><creator>Li, Wenhua</creator><creator>Li, Jian</creator><creator>Wang, Yunchao</creator><creator>Zhang, Keqian</creator><creator>Li, Ni</creator><creator>Tian, Zhiqiang</creator><creator>Ni, Bing</creator><creator>Wang, Huaizhi</creator><creator>Ruan, Zhihua</creator><general>Impact Journals LLC</general><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20161206</creationdate><title>Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma</title><author>Li, Wenhua ; Li, Jian ; Wang, Yunchao ; Zhang, Keqian ; Li, Ni ; Tian, Zhiqiang ; Ni, Bing ; Wang, Huaizhi ; Ruan, Zhihua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-625b72937b89370be9d66fa0b7c52d5495ea0fe8cb47b71d3753c145d93f5f423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - radiation effects</topic><topic>Carcinoma - enzymology</topic><topic>Carcinoma - genetics</topic><topic>Carcinoma - pathology</topic><topic>Carcinoma - therapy</topic><topic>Caspase 3 - metabolism</topic><topic>Cell Cycle Checkpoints - drug effects</topic><topic>Cell Cycle Checkpoints - radiation effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Proliferation - radiation effects</topic><topic>Chemoradiotherapy</topic><topic>Dose-Response Relationship, Drug</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Female</topic><topic>Fingolimod Hydrochloride - pharmacology</topic><topic>Humans</topic><topic>Ki-67 Antigen - metabolism</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Molecular Targeted Therapy</topic><topic>Nasopharyngeal Carcinoma</topic><topic>Nasopharyngeal Neoplasms - enzymology</topic><topic>Nasopharyngeal Neoplasms - genetics</topic><topic>Nasopharyngeal Neoplasms - pathology</topic><topic>Nasopharyngeal Neoplasms - therapy</topic><topic>Phosphorylation</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - genetics</topic><topic>Phosphotransferases (Alcohol Group Acceptor) - metabolism</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Research Paper</topic><topic>RNA Interference</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - radiation effects</topic><topic>Time Factors</topic><topic>Transfection</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>online_resources</toplevel><creatorcontrib>Li, Wenhua</creatorcontrib><creatorcontrib>Li, Jian</creatorcontrib><creatorcontrib>Wang, Yunchao</creatorcontrib><creatorcontrib>Zhang, Keqian</creatorcontrib><creatorcontrib>Li, Ni</creatorcontrib><creatorcontrib>Tian, Zhiqiang</creatorcontrib><creatorcontrib>Ni, Bing</creatorcontrib><creatorcontrib>Wang, Huaizhi</creatorcontrib><creatorcontrib>Ruan, Zhihua</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Wenhua</au><au>Li, Jian</au><au>Wang, Yunchao</au><au>Zhang, Keqian</au><au>Li, Ni</au><au>Tian, Zhiqiang</au><au>Ni, Bing</au><au>Wang, Huaizhi</au><au>Ruan, Zhihua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2016-12-06</date><risdate>2016</risdate><volume>7</volume><issue>49</issue><spage>80586</spage><epage>80598</epage><pages>80586-80598</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Sphingosine kinase 1 (SPHK1) has been shown to be involved in the progression of various types of human cancers. We previously demonstrated that SPHK1 is overexpressed and associated with clinical stage, locoregional recurrence, distant metastasis and poor prognosis in nasopharyngeal carcinoma (NPC). However, the biological roles involving SPHK1 and its potential usefulness as a therapeutic target in NPC remain unknown. In this study, Blocking SPHK1 using siRNA or FTY720 (a SPHK1 inhibitor) significantly reduced proliferation and migration and increased cell cycle arrest and apoptosis in NPC cells. FTY720 also decreased SPHK1 activity, and overexpressing SPHK1 abrogated the FTY720-induced effects on cell viability. In addition, FTY720 sensitized NPC cells to radiotherapy by inhibiting SPHK1 activity in vitro and in vivo. Furthermore, high SPHK1 expression was associated with increased Ki-67 and p-Akt and decreased caspase-3 expression in human NPC specimens. These data suggest that SPHK1 might be a potential therapeutic target for NPC.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>27811359</pmid><doi>10.18632/oncotarget.13014</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncotarget, 2016-12, Vol.7 (49), p.80586-80598 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free E- Journals; PubMed Central Open Access |
| subjects | Animals Antineoplastic Agents - pharmacology Apoptosis - drug effects Apoptosis - radiation effects Carcinoma - enzymology Carcinoma - genetics Carcinoma - pathology Carcinoma - therapy Caspase 3 - metabolism Cell Cycle Checkpoints - drug effects Cell Cycle Checkpoints - radiation effects Cell Line, Tumor Cell Movement - drug effects Cell Proliferation - drug effects Cell Proliferation - radiation effects Chemoradiotherapy Dose-Response Relationship, Drug Dose-Response Relationship, Radiation Female Fingolimod Hydrochloride - pharmacology Humans Ki-67 Antigen - metabolism Mice, Inbred BALB C Mice, Nude Molecular Targeted Therapy Nasopharyngeal Carcinoma Nasopharyngeal Neoplasms - enzymology Nasopharyngeal Neoplasms - genetics Nasopharyngeal Neoplasms - pathology Nasopharyngeal Neoplasms - therapy Phosphorylation Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors Phosphotransferases (Alcohol Group Acceptor) - genetics Phosphotransferases (Alcohol Group Acceptor) - metabolism Protein Kinase Inhibitors - pharmacology Proto-Oncogene Proteins c-akt - metabolism Research Paper RNA Interference Signal Transduction - drug effects Signal Transduction - radiation effects Time Factors Transfection Xenograft Model Antitumor Assays |
| title | Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma |
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