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Prostaglandin E2 Exposure Disrupts E-Cadherin/Caveolin-1-Mediated Tumor Suppression to Favor Caveolin-1-Enhanced Migration, Invasion, and Metastasis in Melanoma Models
(2023)
Lorena Lobos-González
;
Lorena Oróstica
;
Natalia Díaz-Valdivia
;
Victoria Rojas-Celis
;
America Campos
<jats:p>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.</jats:p>
1Scopus© Citations 5
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Src-family kinase inhibitors block early steps of caveolin-1-enhanced lung metastasis by melanoma cells
(2020)
Rina Ortiz
;
Jorge Díaz
;
Natalia Díaz-Valdivia
;
Samuel Martínez
;
Layla Simón
Scopus© Citations 15 1
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Unusual Clinical Presentations of Malignant Melanoma: A Review of Clinical and Histologic Features with Special Emphasis on Dermatoscopic Findings
(2018)
CABRERA MORAGA, RAUL ALEJANDRO
;
Francisca Recule
5Scopus© Citations 106
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Access to innovative medicines for metastatic melanoma worldwide: Melanoma World Society and European Association of Dermato-oncology survey in 34 countries
(2018)
L. Kandolf Sekulovic
;
J. Guo
;
S. Agarwala
;
A. Hauschild
;
G. McArthur
1Scopus© Citations 46
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Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study
(2019)
Georgina V Long
;
Reinhard Dummer
;
Omid Hamid
;
Thomas F Gajewski
;
Christian Caglevic
Scopus© Citations 731 3

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