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E-cadherin is important in CAV1-dependent tumor suppression and prevents CAV1-enhanced lung metastasis. Here, we used murine B16F10 and human A375 melanoma cells with low levels of endogenous CAV1 and E-cadherin to unravel how co-expression of E-cadherin modulates CAV1 function in vitro and in vivo in WT C57BL\/6 or Rag\u2212\/\u2212 immunodeficient mice and how a pro-inflammatory environment generated by treating cells with prostaglandin E2 (PGE2) alters CAV1 function in the presence of E-cadherin. CAV1 expression augmented migration, invasion, and metastasis of melanoma cells, and these effects were abolished via transient co-expression of E-cadherin. Importantly, exposure of cells to PGE2 reverted the effects of E-cadherin expression and increased CAV1 phosphorylation on tyrosine-14 and metastasis. Moreover, PGE2 administration blocked the ability of the CAV1\/E-cadherin complex to prevent tumor formation. Therefore, our results support the notion that PGE2 can override the tumor suppressor potential of the E-cadherin\/CAV1 complex and that CAV1 released from the complex is phosphorylated on tyrosine-14 and promotes migration\/invasion\/metastasis. These observations provide direct evidence showing how a pro-inflammatory environment caused here via PGE2 administration can convert a potent tumor suppressor complex into a promoter of malignant cell behavior.<\/jats:p>","DOI":"10.3390\/ijms242316947","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T12:01:00Z","timestamp":1701259260000},"page":"16947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Prostaglandin E2 Exposure Disrupts E-Cadherin\/Caveolin-1-Mediated Tumor Suppression to Favor Caveolin-1-Enhanced Migration, Invasion, and Metastasis in Melanoma Models"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4957-9864","authenticated-orcid":false,"given":"Lorena","family":"Lobos-Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Centro de Medicina Regenerativa, Facultad de Medicina-Cl\u00ednica Alemana, Universidad del Desarrollo, Avenida Lo Plaza 680, Las Condes 7610658, Chile"},{"name":"Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Universidad de Chile, Santiago 8380494, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9563-4318","authenticated-orcid":false,"given":"Lorena","family":"Or\u00f3stica","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Communication, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Program of Cell and Molecular Biology, Biomedical Sciences Institute (ICBM), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica, Facultad de Medicina, Universidad Diego Portales, Santiago 8370007, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8063-2598","authenticated-orcid":false,"given":"Natalia","family":"D\u00edaz-Valdivia","sequence":"additional","affiliation":[{"name":"Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Universidad de Chile, Santiago 8380494, Chile"},{"name":"Laboratory of Cellular Communication, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Program of Cell and Molecular Biology, Biomedical Sciences Institute (ICBM), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Rojas-Celis","sequence":"additional","affiliation":[{"name":"Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Universidad de Chile, Santiago 8380494, Chile"},{"name":"Laboratory of Cellular Communication, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Program of Cell and Molecular Biology, Biomedical Sciences Institute (ICBM), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"America","family":"Campos","sequence":"additional","affiliation":[{"name":"Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Universidad de Chile, Santiago 8380494, Chile"},{"name":"CRUK Scotland Institute, Glasgow G61 1BD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6974-7004","authenticated-orcid":false,"given":"Eduardo","family":"Duran-Jara","sequence":"additional","affiliation":[{"name":"Centro de Medicina Regenerativa, Facultad de Medicina-Cl\u00ednica Alemana, Universidad del Desarrollo, Avenida Lo Plaza 680, Las Condes 7610658, Chile"},{"name":"Subdepartamento Gen\u00e9tica Molecular, Instituto de Salud P\u00fablica de Chile, Santiago 7780050, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Farf\u00e1n","sequence":"additional","affiliation":[{"name":"Cancer and ncRNAs Laboratory, Universidad Andres Bello, Santiago 7550611, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisette","family":"Leyton","sequence":"additional","affiliation":[{"name":"Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Universidad de Chile, Santiago 8380494, Chile"},{"name":"Laboratory of Cellular Communication, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Program of Cell and Molecular Biology, Biomedical Sciences Institute (ICBM), Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew F. 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