Publication:
Prostaglandin E2 Exposure Disrupts E-Cadherin/Caveolin-1-Mediated Tumor Suppression to Favor Caveolin-1-Enhanced Migration, Invasion, and Metastasis in Melanoma Models

dc.contributor.authorLobos-González, Lorena
dc.contributor.authorOróstica, Lorena
dc.contributor.authorDíaz, Natalia
dc.contributor.authorRojas, Victoria
dc.contributor.authorCampos, America
dc.contributor.authorDuran, Eduardo
dc.contributor.authorFarfán, Nicole
dc.contributor.authorFarfán, Nicole
dc.contributor.authorLeyton, Lisette
dc.contributor.authorQuest, Andrew
dc.date.accessioned2024-05-30T19:32:28Z
dc.date.available2024-05-30T19:32:28Z
dc.date.issued2023
dc.description.abstractCaveolin-1 (CAV1) is a membrane-bound protein that suppresses tumor development yet also promotes metastasis. 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-/- 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.
dc.description.versionPublicada
dc.identifier.citationLobos-González L, Oróstica L, Díaz-Valdivia N, Rojas-Celis V, Campos A, Duran-Jara E, Farfán N, Leyton L, Quest AFG. Prostaglandin E2 Exposure Disrupts E-Cadherin/Caveolin-1-Mediated Tumor Suppression to Favor Caveolin-1-Enhanced Migration, Invasion, and Metastasis in Melanoma Models. Int J Mol Sci. 2023 Nov 29;24(23):16947. doi: 10.3390/ijms242316947
dc.identifier.doihttps://doi.org/10.3390/ijms242316947
dc.identifier.urihttps://hdl.handle.net/11447/8966
dc.language.isoen
dc.subjectCaveolin-1
dc.subjectE-cadherin
dc.subjectPGE2
dc.subjectinflammation
dc.subjecttumor progression
dc.titleProstaglandin E2 Exposure Disrupts E-Cadherin/Caveolin-1-Mediated Tumor Suppression to Favor Caveolin-1-Enhanced Migration, Invasion, and Metastasis in Melanoma Models
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceInternational journal of molecular sciences
dspace.entity.typePublication

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