Celia Sequera, Sara Manzano, Carmen Guerrero, Almudena Porras
{"title":"Rap及其gef如何控制肝脏生理和癌症发展。C3G在人肝癌中的改变。","authors":"Celia Sequera, Sara Manzano, Carmen Guerrero, Almudena Porras","doi":"10.2217/hep-2017-0026","DOIUrl":null,"url":null,"abstract":"<p><p>Rap proteins regulate liver physiopathology. For example, Rap2B promotes hepatocarcinoma (HCC) growth, while Rap1 might play a dual role. The RapGEF, Epac1, activates Rap upon cAMP binding, regulating metabolism, survival, and liver regeneration. A liver specific Epac2 isoform lacking cAMP-binding domain also activates Rap1, promoting fibrosis in alcoholic liver disease. C3G (RapGEF1) is also present in the liver, but mainly as shorter isoforms. Its function in the liver remains unknown. Information from different public genetic databases revealed that C3G mRNA levels increase in HCC, although they decrease in metastatic stages. In addition, several mutations in RapGEF1 gene are present, associated with a reduced patient survival. Based on this, C3G might represent a new HCC diagnostic and prognostic marker, and a therapeutic target.</p>","PeriodicalId":44854,"journal":{"name":"Hepatic Oncology","volume":"5 1","pages":"HEP05"},"PeriodicalIF":1.2000,"publicationDate":"2018-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/hep-2017-0026","citationCount":"22","resultStr":"{\"title\":\"How Rap and its GEFs control liver physiology and cancer development. C3G alterations in human hepatocarcinoma.\",\"authors\":\"Celia Sequera, Sara Manzano, Carmen Guerrero, Almudena Porras\",\"doi\":\"10.2217/hep-2017-0026\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Rap proteins regulate liver physiopathology. For example, Rap2B promotes hepatocarcinoma (HCC) growth, while Rap1 might play a dual role. The RapGEF, Epac1, activates Rap upon cAMP binding, regulating metabolism, survival, and liver regeneration. A liver specific Epac2 isoform lacking cAMP-binding domain also activates Rap1, promoting fibrosis in alcoholic liver disease. C3G (RapGEF1) is also present in the liver, but mainly as shorter isoforms. Its function in the liver remains unknown. Information from different public genetic databases revealed that C3G mRNA levels increase in HCC, although they decrease in metastatic stages. In addition, several mutations in RapGEF1 gene are present, associated with a reduced patient survival. Based on this, C3G might represent a new HCC diagnostic and prognostic marker, and a therapeutic target.</p>\",\"PeriodicalId\":44854,\"journal\":{\"name\":\"Hepatic Oncology\",\"volume\":\"5 1\",\"pages\":\"HEP05\"},\"PeriodicalIF\":1.2000,\"publicationDate\":\"2018-04-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.2217/hep-2017-0026\",\"citationCount\":\"22\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hepatic Oncology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2217/hep-2017-0026\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2018/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatic Oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2217/hep-2017-0026","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2018/1/1 0:00:00","PubModel":"eCollection","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
How Rap and its GEFs control liver physiology and cancer development. C3G alterations in human hepatocarcinoma.
Rap proteins regulate liver physiopathology. For example, Rap2B promotes hepatocarcinoma (HCC) growth, while Rap1 might play a dual role. The RapGEF, Epac1, activates Rap upon cAMP binding, regulating metabolism, survival, and liver regeneration. A liver specific Epac2 isoform lacking cAMP-binding domain also activates Rap1, promoting fibrosis in alcoholic liver disease. C3G (RapGEF1) is also present in the liver, but mainly as shorter isoforms. Its function in the liver remains unknown. Information from different public genetic databases revealed that C3G mRNA levels increase in HCC, although they decrease in metastatic stages. In addition, several mutations in RapGEF1 gene are present, associated with a reduced patient survival. Based on this, C3G might represent a new HCC diagnostic and prognostic marker, and a therapeutic target.
期刊介绍：
Primary liver cancer is the sixth most common cancer in the world, and the third most common cause of death from malignant disease. Traditionally more common in developing countries, hepatocellular carcinoma is becoming increasingly prevalent in the Western world, primarily due to an increase in hepatitis C virus infection. Emerging risk factors, such as non-alcoholic fatty liver disease and obesity are also of concern for the future. In addition, metastatic tumors of the liver are more common than primary disease. Some studies report hepatic metastases in as many as 40 to 50% of adult patients with extrahepatic primary tumors. Hepatic Oncology publishes original research studies and reviews addressing preventive, diagnostic and therapeutic approaches to all types of cancer of the liver, in both the adult and pediatric populations. The journal also highlights significant advances in basic and translational research, and places them in context for future therapy. Hepatic Oncology provides a forum to report and debate all aspects of cancer of the liver and bile ducts. The journal publishes original research studies, full reviews and commentaries, with all articles subject to independent review by a minimum of three independent experts. Unsolicited article proposals are welcomed and authors are required to comply fully with the journal''s Disclosure & Conflict of Interest Policy as well as major publishing guidelines, including ICMJE and GPP3.
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