title: Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas.
abstract: 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.
authors: Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas "Alberto Sols", CSIC-UAM, IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain. gmoreno@iib.uam.es
authors: Gema
authors: G
authors: Moreno-Bueno
authors: Fernando
authors: F
authors: Salvador
authors: Alberto
authors: A
authors: Martín
authors: Alfredo
authors: A
authors: Floristán
authors: Eva P
authors: EP
authors: Cuevas
authors: Vanesa
authors: V
authors: Santos
authors: Amalia
authors: A
authors: Montes
authors: Saleta
authors: S
authors: Morales
authors: Maria Angeles
authors: MA
authors: Castilla
authors: Alejandro
authors: A
authors: Rojo-Sebastián
authors: Alejandra
authors: A
authors: Martínez
authors: David
authors: D
authors: Hardisson
authors: Katalin
authors: K
authors: Csiszar
authors: Francisco
authors: F
authors: Portillo
authors: Héctor
authors: H
authors: Peinado
authors: José
authors: J
authors: Palacios
authors: Amparo
authors: A
authors: Cano
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology* / Q000556:secondary*; D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D015415:Biomarkers; D001943:Breast Neoplasms / Q000469:parasitology* / Q000556:secondary*; D016764:Cell Polarity; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis / Q000473:pathology*
chemical_list: D015415:Biomarkers; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human