Isoprenaline induces epithelial-mesenchymal transition in gastric cancer cells.
Mol Cell Biochem
; 408(1-2): 1-13, 2015 Oct.
Article
en En
| MEDLINE
| ID: mdl-26253173
The emerging role of stress-related signaling in regulating cancer development and progression has been recognized. However, whether stress serves as a mechanism to promote gastric cancer metastasis is not clear. Here, we show that the ß2-AR agonist, isoprenaline, upregulates expression levels of CD44 and CD44v8-10 in gastric cancer cells. CD44, a cancer stem cell-related marker, is expressed at high levels in gastric cancer tissues, which strongly correlates with the occurrence of epithelial-mesenchymal transition (EMT)-associated phenotypes both in vivo and in vitro. Combined with experimental observations in two human gastric cancer cell lines, we found that ß2-AR signaling can initiate EMT. It led to an increased expression of mesenchymal markers, such as α-SMA, vimentin, and snail at mRNA and protein levels, and conversely a decrease in epithelial markers, E-cadherin and ß-catenin. Isoprenaline stimulation of ß2-AR receptors activates the downstream target STAT3, which functions as a positive regulator and mediated the phenotypic switch toward a mesenchymal cell type in gastric cancer cells. Our data provide a mechanistic understanding of the complex signaling cascades involving stress-related hormones and their effects on EMT. In light of our observations, pharmacological interventions targeting ß2-AR-STAT3 signaling can potentially be used to ameliorate stress-associated influences on gastric cancer development and progression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
/
Agonistas Adrenérgicos beta
/
Transición Epitelial-Mesenquimal
/
Isoproterenol
Límite:
Humans
Idioma:
En
Revista:
Mol Cell Biochem
Año:
2015
Tipo del documento:
Article
Pais de publicación:
Países Bajos