| Autor: | Lobos-González, Lorena, Oróstica, Lorena, Díaz-Valdivia, Natalia, Rojas-Celis, Victoria, Campos, America, Duran-Jara, Eduardo, Farfán, Nicole, Leyton, Lisette, Quest, Andrew F. G. |
| Revista: | International Journal of Molecular Sciences |
| Año: | 2023 |
| Número: | 23 |
| Paginas: | 16947 |
| Volumen: | 24 |
| Abstract: | Caveolin-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. |
| Idioma: | eng |
| Base de Datos: | PubMed |
| Ver Más: | https://doi.org/10.3390/ijms242316947 |