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However, the precise function of Rap1A in ovarian cancer is still not understood. Here, we show that Rap1A promotes ovarian cancer tumorigenesis and metastasis via stimulating cell proliferation, migration and invasion both in vivo and in vitro. Mechanistic study showed that Rap1A activates extracellular signal\u2010regulated kinase (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>), p38 mitogen\u2010activated protein kinase (<jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content>) and Notch pathways, leading to the enhanced expression of several epithelial\u2010mesenchymal transition (<jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content>) markers such as slug, zeb1, vimentin, fibronectin, and <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>9. However, the pretreatment of Rap1A\u2010overexpressing cells with the Notch inhibitor <jats:styled-content style=\"fixed-case\">DAPT<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> inhibitor (U0126) inhibited the up\u2010regulated expression of those molecules. These findings provide the first evidence linking Rap1A with ovarian cancer development through the <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\/p38 and Notch signaling pathways, indicating that Rap1A may be used as a novel diagnostic marker or a therapeutic target for ovarian cancer.<\/jats:p>","DOI":"10.1002\/cam4.946","type":"journal-article","created":{"date-parts":[[2016,11,5]],"date-time":"2016-11-05T04:10:07Z","timestamp":1478319007000},"page":"3544-3554","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Rap1A promotes ovarian cancer metastasis via activation of ERK\/p38 and notch signaling"],"prefix":"10.1002","volume":"5","author":[{"given":"Lili","family":"Lu","sequence":"first","affiliation":[{"name":"Cancer Institute Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical School Fudan University  Shanghai 200032 China"},{"name":"Department of Biology College of Life and Environmental Sciences Shanghai Normal University  100 Guilin Road Shanghai 200234 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingshu","family":"Wang","sequence":"additional","affiliation":[{"name":"Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yougen","family":"Wu","sequence":"additional","affiliation":[{"name":"Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Biology College of Life and Environmental Sciences Shanghai Normal University  100 Guilin Road Shanghai 200234 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong","family":"Yang","sequence":"additional","affiliation":[{"name":"Cancer Institute Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical School Fudan University  Shanghai 200032 China"},{"name":"Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University  Shanghai 200240 China"},{"name":"Department of Gynecological Oncology, The Fifth People's Hospital of Shanghai Fudan University  Shanghai 200240 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