Prostaglandin E2 Exposure Disrupts E-Cadherin/Caveolin-1-Mediated Tumor Suppression to Favor Caveolin-1-Enhanced Migration, Invasion, and Metastasis in Melanoma Models
Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Date Issued
2023
Author(s)
Lorena Lobos-González
Lorena Oróstica
Natalia Díaz-Valdivia
Victoria Rojas-Celis
America Campos
Eduardo Duran-Jara
Nicole Farfán
Lisette Leyton
Andrew F. G. Quest
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<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>
Cite this document
Lobos-González, L., Oróstica, L., Díaz-Valdivia, N., Rojas-Celis, V., Campos, A., Duran-Jara, E., Farfán, N., Leyton, L., & Quest, A. F. G. (2023). Prostaglandin e2 exposure disrupts e-cadherin/caveolin-1-mediated tumor suppression to favor caveolin-1-enhanced migration, invasion, and metastasis in melanoma models. International Journal of Molecular Sciences, 24(23), 16947. https://doi.org/10.3390/ijms242316947
Subjects
caveolin-1
;
e-cadherin
;
inflammation
;
pge2
;
tumor progression
;
animals
;
cadherins
;
caveolin 1
;
cell line, tumor
;
cell movement
;
dinoprostone
;
humans
;
melanoma, experimental
;
mice
;
mice, inbred c57bl
;
neoplasm metastasis
;
tyrosine
;
caveolin 1
;
prostaglandin e2
;
tyrosine
;
uvomorulin
;
cadherin
;
caveolin 1
;
prostaglandin e2
;
tyrosine
;
a-375 cell line
;
adult
;
animal cell
;
animal experiment
;
animal model
;
animal tissue
;
article
;
b16-f10 cell line
;
cancer inhibition
;
cancer model
;
controlled study
;
human
;
human cell
;
in vitro study
;
in vivo study
;
metastatic melanoma
;
mouse
;
nonhuman
;
protein expression
;
protein phosphorylation
;
tumor invasion
;
animal
;
c57bl mouse
;
cell motion
;
experimental melanoma
;
metabolism
;
metastasis
;
pathology
;
tumor cell line