IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
ROR1 contributes to melanoma cell growth and migration by regulating N-cadherin expression via the PI3K/Akt pathway
Autor/es:
FERNÁNDEZ NB; LORENZO D; PICCO ME; BARBERO G; DERGAN-DYLON LS; MARKS MP; GARCÍA-RIVELLO H; GIMENEZ L; LABOVSKY V; GRUMOLATO L; LOPEZ-BERGAMI P
Revista:
MOLECULAR CARCINOGENESIS.
Editorial:
WILEY-LISS, DIV JOHN WILEY & SONS INC
Referencias:
Lugar: New York; Año: 2015
ISSN:
0899-1987
Resumen:
The Receptor tyrosine kinase-like Orphan Receptor 1 (ROR1) is primarily expressed by neural crest cells duringembryogenesis. Following a complete downregulation after birth, ROR1 was shown to re-express in various types ofcancers. Little is known about ROR1 expression and function in melanoma. Here we show that ROR1 is aberrantlyexpressed in both melanoma cell lines and tumors and that its expression associates with poor Post-Recurrence Survival ofmelanoma. Using gain- and loss-of-function approaches we found that ROR1 enhances both anchorage-dependent and-independent growth of melanoma cells. In addition, ROR1 decreases cell adhesion and increases cell motility andmigration. Mechanistically, ROR1 was found to induce upregulation of Akt and the mesenquimal markers N-cadherinand vimentin. The regulation of N-cadherin by ROR1 relies on both Akt dependent and independent mechanisms. ROR1does not affect Wnt canonical pathway but was found to be engaged in a positive feedback loop with Wnt5a. In summary,we show that ROR1 contributes to melanoma progression and is a candidate biomarker of poor prognosis. Althoughfurther studies are needed to confirm this possibility, the present work indicates that ROR1 is a good prospective target formelanoma cancer therapy.