{"title":"达帕格列净通过调节 OTUD5 介导的 YAP1 去泛素化抑制胃癌生长","authors":"","doi":"10.1016/j.ejphar.2024.177002","DOIUrl":null,"url":null,"abstract":"<div><p>Gastric cancer (GC) is a common malignant disease that has a fifth highest incidence and fourth highest mortality worldwide. The Warburg effect is a common phenomenon observed in tumors, which suggests that tumor cells would enhance glucose uptake by overexpressing multiple glucose transporters. Sodium glucose transporter 2 (SGLT2) is one of glucose transporters which highly expressed in several cancers, but its role in gastric cancer is still unclear. Our research found that there was a high expression level of SGLT2 in gastric cancer tissues. We found that Dapagliflozin (a SGLT2 inhibitor) could suppress gastric cancer cell proliferation and migration <em>in vitro</em> and tumor growth <em>in vivo</em>. In present study, we revealed how dapagliflozin would suppress gastric cancer progression in a novel mechanism. We proved that dapagliflozin decreased the expression level of OTU deubiquitinase 5 (OTUD5), which further increased the ubiquitination and degradation of YAP1. Overexpression of OTUD5 in gastric cancer cells partly reversed the anti-tumor effect of dapagliflozin. Our findings revealed a novel mechanism by which dapagliflozin has an antitumor effect on gastric cancer and proposed a beneficial strategy for the application of dapagliflozin in gastric cancer patients.</p></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014299924006927/pdfft?md5=2ef2da1713c7aada7a585612674786dc&pid=1-s2.0-S0014299924006927-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Dapagliflozin suppressed gastric cancer growth via regulating OTUD5 mediated YAP1 deubiquitination\",\"authors\":\"\",\"doi\":\"10.1016/j.ejphar.2024.177002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Gastric cancer (GC) is a common malignant disease that has a fifth highest incidence and fourth highest mortality worldwide. The Warburg effect is a common phenomenon observed in tumors, which suggests that tumor cells would enhance glucose uptake by overexpressing multiple glucose transporters. Sodium glucose transporter 2 (SGLT2) is one of glucose transporters which highly expressed in several cancers, but its role in gastric cancer is still unclear. Our research found that there was a high expression level of SGLT2 in gastric cancer tissues. We found that Dapagliflozin (a SGLT2 inhibitor) could suppress gastric cancer cell proliferation and migration <em>in vitro</em> and tumor growth <em>in vivo</em>. In present study, we revealed how dapagliflozin would suppress gastric cancer progression in a novel mechanism. We proved that dapagliflozin decreased the expression level of OTU deubiquitinase 5 (OTUD5), which further increased the ubiquitination and degradation of YAP1. Overexpression of OTUD5 in gastric cancer cells partly reversed the anti-tumor effect of dapagliflozin. Our findings revealed a novel mechanism by which dapagliflozin has an antitumor effect on gastric cancer and proposed a beneficial strategy for the application of dapagliflozin in gastric cancer patients.</p></div>\",\"PeriodicalId\":12004,\"journal\":{\"name\":\"European journal of pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.2000,\"publicationDate\":\"2024-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0014299924006927/pdfft?md5=2ef2da1713c7aada7a585612674786dc&pid=1-s2.0-S0014299924006927-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European journal of pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0014299924006927\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014299924006927","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Dapagliflozin suppressed gastric cancer growth via regulating OTUD5 mediated YAP1 deubiquitination
Gastric cancer (GC) is a common malignant disease that has a fifth highest incidence and fourth highest mortality worldwide. The Warburg effect is a common phenomenon observed in tumors, which suggests that tumor cells would enhance glucose uptake by overexpressing multiple glucose transporters. Sodium glucose transporter 2 (SGLT2) is one of glucose transporters which highly expressed in several cancers, but its role in gastric cancer is still unclear. Our research found that there was a high expression level of SGLT2 in gastric cancer tissues. We found that Dapagliflozin (a SGLT2 inhibitor) could suppress gastric cancer cell proliferation and migration in vitro and tumor growth in vivo. In present study, we revealed how dapagliflozin would suppress gastric cancer progression in a novel mechanism. We proved that dapagliflozin decreased the expression level of OTU deubiquitinase 5 (OTUD5), which further increased the ubiquitination and degradation of YAP1. Overexpression of OTUD5 in gastric cancer cells partly reversed the anti-tumor effect of dapagliflozin. Our findings revealed a novel mechanism by which dapagliflozin has an antitumor effect on gastric cancer and proposed a beneficial strategy for the application of dapagliflozin in gastric cancer patients.
期刊介绍:
The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems.
The scope includes:
Behavioural pharmacology
Neuropharmacology and analgesia
Cardiovascular pharmacology
Pulmonary, gastrointestinal and urogenital pharmacology
Endocrine pharmacology
Immunopharmacology and inflammation
Molecular and cellular pharmacology
Regenerative pharmacology
Biologicals and biotherapeutics
Translational pharmacology
Nutriceutical pharmacology.