Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas.

Basal-like breast carcinoma is characterized by the expression of basal/myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and frequent triple negative status (ESR-, PR-, Her2neu-). We have previously shown that epithelial-mesenchymal transition (EMT) occurs in basal-like...

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Detalles Bibliográficos
Autores: Moreno-Bueno, Gema, Salvador, Fernando, Martín, Alberto, Floristán, Alfredo, Cuevas, Eva P, Santos, Vanesa, Montes, Amalia, Morales, Saleta, Castilla, Maria Angeles, Rojo-Sebastián, Alejandro, Martínez, Alejandra, Hardisson, David, Csiszar, Katalin, Portillo, Francisco, Peinado, Héctor, Palacios, José, Cano, Amparo
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17966
Acceso en línea:http://hdl.handle.net/20.500.12105/17966
Access Level:acceso abierto
Palabra clave:Cell Polarity
Adenocarcinoma
Amino Acid Oxidoreductases
Biomarkers
Breast Neoplasms
Female
Humans
Neoplasm Metastasis
Descripción
Sumario:Basal-like breast carcinoma is characterized by the expression of basal/myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and frequent triple negative status (ESR-, PR-, Her2neu-). We have previously shown that epithelial-mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl-oxidase-like 2 (LOXL2) as an EMT player and poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Breast carcinoma cell lines with basal-like phenotype show a specific cytoplasmic/perinuclear LOXL2 expression, and this subcellular distribution is significantly associated with distant metastatic incidence in basal-like breast carcinomas. LOXL2 silencing in basal-like carcinoma cells induces a mesenchymal-epithelial transition (MET) associated with a decrease of tumourigenicity and suppression of metastatic potential. Mechanistic studies indicate that LOXL2 maintains the mesenchymal phenotype of basal-like carcinoma cells by a novel mechanism involving transcriptional downregulation of Lgl2 and claudin1 and disorganization of cell polarity and tight junction complexes. Therefore, intracellular LOXL2 is a new candidate marker of basal-like carcinomas and a target to block metastatic dissemination of this aggressive breast tumour subtype.

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