Enolase 1 stimulates glycolysis to promote chemoresistance in gastric cancer
Chemotherapy is the major choice for the cancer treatment of early and advanced stages. However, intrinsic or acquired drug resistance significantly restricts the clinical efficacy of chemotherapy. It is critical to develop novel approaches to detect and overcome drug resistance. In this study, we d...
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| Veröffentlicht in: | Oncotarget 2017-07, Vol.8 (29), p.47691-47708 |
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| creator | Qian, Xiaoling Xu, Wenxia Xu, Jinye Shi, Qiqi Li, Jiaqiu Weng, Yu Jiang, Zhinong Feng, Lifeng Wang, Xian Zhou, Jianwei Jin, Hongchuan |
| description | Chemotherapy is the major choice for the cancer treatment of early and advanced stages. However, intrinsic or acquired drug resistance significantly restricts the clinical efficacy of chemotherapy. It is critical to develop novel approaches to detect and overcome drug resistance. In this study, we demonstrated that accelerated glycolysis played a pivotal role in both intrinsic and acquired cisplatin-resistance of gastric cancer cells. The metabolic reprogramming of cisplatin-resistant cells was characterized by increased glycolysis dependence. Inhibition of glycolysis with glucose starvation or 2-Deoxy-D-glucose (2-DG) treatment significantly reversed drug resistance. By proteomic screening, we found the increased expression of the glycolytic enzyme Enolase 1 (ENO1) in cisplatin-resistant gastric cancer cells. Depletion of ENO1 by siRNA significantly reduced glycolysis and reversed drug resistance. Moreover, the increased expression of ENO1 was attributed to the down-regulation of ENO1-targeting miR-22, rather than activated gene transcriptional or prolonged protein stability. Finally, the elevated levels of ENO1 proteins were associated with the shorter overall survival of gastric cancer patients. In conclusion, ENO1 is a novel biomarker to predict drug resistance and overall prognosis in gastric cancer. Targeting ENO1 by chemical inhibitors or up-regulating miR-22 could be valuable to overcome drug resistance. |
| doi_str_mv | 10.18632/oncotarget.17868 |
| format | Article |
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However, intrinsic or acquired drug resistance significantly restricts the clinical efficacy of chemotherapy. It is critical to develop novel approaches to detect and overcome drug resistance. In this study, we demonstrated that accelerated glycolysis played a pivotal role in both intrinsic and acquired cisplatin-resistance of gastric cancer cells. The metabolic reprogramming of cisplatin-resistant cells was characterized by increased glycolysis dependence. Inhibition of glycolysis with glucose starvation or 2-Deoxy-D-glucose (2-DG) treatment significantly reversed drug resistance. By proteomic screening, we found the increased expression of the glycolytic enzyme Enolase 1 (ENO1) in cisplatin-resistant gastric cancer cells. Depletion of ENO1 by siRNA significantly reduced glycolysis and reversed drug resistance. Moreover, the increased expression of ENO1 was attributed to the down-regulation of ENO1-targeting miR-22, rather than activated gene transcriptional or prolonged protein stability. Finally, the elevated levels of ENO1 proteins were associated with the shorter overall survival of gastric cancer patients. In conclusion, ENO1 is a novel biomarker to predict drug resistance and overall prognosis in gastric cancer. Targeting ENO1 by chemical inhibitors or up-regulating miR-22 could be valuable to overcome drug resistance.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.17868</identifier><identifier>PMID: 28548950</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Antineoplastic Agents - pharmacology ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Cell Line, Tumor ; Cisplatin - pharmacology ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Drug Resistance, Neoplasm - genetics ; Female ; Gene Expression ; Gene Knockdown Techniques ; Glycolysis - drug effects ; Humans ; Male ; MicroRNAs - genetics ; Neoplasm Grading ; Neoplasm Staging ; Phosphopyruvate Hydratase - genetics ; Phosphopyruvate Hydratase - metabolism ; Prognosis ; Proportional Hazards Models ; Research Paper ; RNA Interference ; RNA, Messenger - genetics ; Stomach Neoplasms - genetics ; Stomach Neoplasms - metabolism ; Stomach Neoplasms - mortality ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism</subject><ispartof>Oncotarget, 2017-07, Vol.8 (29), p.47691-47708</ispartof><rights>Copyright: © 2017 Qian et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-3dc44b156671242e1a89dd318562d891dae7d4345a9c174c963beb9b5e5fb8ba3</citedby><cites>FETCH-LOGICAL-c356t-3dc44b156671242e1a89dd318562d891dae7d4345a9c174c963beb9b5e5fb8ba3</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/PMC5564598/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564598/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28548950$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qian, Xiaoling</creatorcontrib><creatorcontrib>Xu, Wenxia</creatorcontrib><creatorcontrib>Xu, Jinye</creatorcontrib><creatorcontrib>Shi, Qiqi</creatorcontrib><creatorcontrib>Li, Jiaqiu</creatorcontrib><creatorcontrib>Weng, Yu</creatorcontrib><creatorcontrib>Jiang, Zhinong</creatorcontrib><creatorcontrib>Feng, Lifeng</creatorcontrib><creatorcontrib>Wang, Xian</creatorcontrib><creatorcontrib>Zhou, Jianwei</creatorcontrib><creatorcontrib>Jin, Hongchuan</creatorcontrib><title>Enolase 1 stimulates glycolysis to promote chemoresistance in gastric cancer</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Chemotherapy is the major choice for the cancer treatment of early and advanced stages. However, intrinsic or acquired drug resistance significantly restricts the clinical efficacy of chemotherapy. It is critical to develop novel approaches to detect and overcome drug resistance. In this study, we demonstrated that accelerated glycolysis played a pivotal role in both intrinsic and acquired cisplatin-resistance of gastric cancer cells. The metabolic reprogramming of cisplatin-resistant cells was characterized by increased glycolysis dependence. Inhibition of glycolysis with glucose starvation or 2-Deoxy-D-glucose (2-DG) treatment significantly reversed drug resistance. By proteomic screening, we found the increased expression of the glycolytic enzyme Enolase 1 (ENO1) in cisplatin-resistant gastric cancer cells. Depletion of ENO1 by siRNA significantly reduced glycolysis and reversed drug resistance. Moreover, the increased expression of ENO1 was attributed to the down-regulation of ENO1-targeting miR-22, rather than activated gene transcriptional or prolonged protein stability. Finally, the elevated levels of ENO1 proteins were associated with the shorter overall survival of gastric cancer patients. In conclusion, ENO1 is a novel biomarker to predict drug resistance and overall prognosis in gastric cancer. Targeting ENO1 by chemical inhibitors or up-regulating miR-22 could be valuable to overcome drug resistance.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cisplatin - pharmacology</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gene Knockdown Techniques</subject><subject>Glycolysis - drug effects</subject><subject>Humans</subject><subject>Male</subject><subject>MicroRNAs - genetics</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Staging</subject><subject>Phosphopyruvate Hydratase - genetics</subject><subject>Phosphopyruvate Hydratase - metabolism</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Research Paper</subject><subject>RNA Interference</subject><subject>RNA, Messenger - genetics</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - metabolism</subject><subject>Stomach Neoplasms - mortality</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - metabolism</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUU1PwzAMjRCITWM_gAvKkUtH0yRtckFC0_iQJnGBc5SmXhfUNiNJkfbvKdsYwxdbz8_Plh9C1ySdEZHT7M51xkXta4gzUohcnKExkUwmGef0_KQeoWkIH-kQnBUik5dolAnOhOTpGC0XnWt0AExwiLbtGx0h4LrZGtdsgw04OrzxrnURsFlD6zwMaNSdAWw7XOsQvTXY_AD-Cl2sdBNgesgT9P64eJs_J8vXp5f5wzIxlOcxoZVhrCQ8zwuSsQyIFrKqKBE8zyohSaWhqBhlXEtDCmZkTksoZcmBr0pRajpB93vdTV-2UBnooteN2njbar9VTlv1v9PZtardl-I8Z1yKQeD2IODdZw8hqtYGA02jO3B9UESmlAzUggxUsqca70LwsDquIanaGaH-jFA7I4aZm9P7jhO_b6ffU5-JKQ</recordid><startdate>20170718</startdate><enddate>20170718</enddate><creator>Qian, Xiaoling</creator><creator>Xu, Wenxia</creator><creator>Xu, Jinye</creator><creator>Shi, Qiqi</creator><creator>Li, Jiaqiu</creator><creator>Weng, Yu</creator><creator>Jiang, Zhinong</creator><creator>Feng, Lifeng</creator><creator>Wang, Xian</creator><creator>Zhou, Jianwei</creator><creator>Jin, Hongchuan</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>20170718</creationdate><title>Enolase 1 stimulates glycolysis to promote chemoresistance in gastric cancer</title><author>Qian, Xiaoling ; 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However, intrinsic or acquired drug resistance significantly restricts the clinical efficacy of chemotherapy. It is critical to develop novel approaches to detect and overcome drug resistance. In this study, we demonstrated that accelerated glycolysis played a pivotal role in both intrinsic and acquired cisplatin-resistance of gastric cancer cells. The metabolic reprogramming of cisplatin-resistant cells was characterized by increased glycolysis dependence. Inhibition of glycolysis with glucose starvation or 2-Deoxy-D-glucose (2-DG) treatment significantly reversed drug resistance. By proteomic screening, we found the increased expression of the glycolytic enzyme Enolase 1 (ENO1) in cisplatin-resistant gastric cancer cells. Depletion of ENO1 by siRNA significantly reduced glycolysis and reversed drug resistance. Moreover, the increased expression of ENO1 was attributed to the down-regulation of ENO1-targeting miR-22, rather than activated gene transcriptional or prolonged protein stability. Finally, the elevated levels of ENO1 proteins were associated with the shorter overall survival of gastric cancer patients. In conclusion, ENO1 is a novel biomarker to predict drug resistance and overall prognosis in gastric cancer. Targeting ENO1 by chemical inhibitors or up-regulating miR-22 could be valuable to overcome drug resistance.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28548950</pmid><doi>10.18632/oncotarget.17868</doi><tpages>18</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antineoplastic Agents - pharmacology Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Cell Line, Tumor Cisplatin - pharmacology DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Drug Resistance, Neoplasm - genetics Female Gene Expression Gene Knockdown Techniques Glycolysis - drug effects Humans Male MicroRNAs - genetics Neoplasm Grading Neoplasm Staging Phosphopyruvate Hydratase - genetics Phosphopyruvate Hydratase - metabolism Prognosis Proportional Hazards Models Research Paper RNA Interference RNA, Messenger - genetics Stomach Neoplasms - genetics Stomach Neoplasms - metabolism Stomach Neoplasms - mortality Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism |
| title | Enolase 1 stimulates glycolysis to promote chemoresistance in gastric cancer |
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