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

Moreno-Bueno, GemaSalvador, FernandoMartín, AlbertoFloristán, AlfredoCuevas, Eva PSantos, VanesaMontes, AmaliaMorales, SaletaCastilla, Maria AngelesRojo-Sebastián, AlejandroMartínez, AlejandraHardisson, DavidCsiszar, KatalinPortillo, FranciscoPeinado, HéctorPalacios, JoséCano, Amparo2024-02-122024-02-122011-09EMBO Mol Med . 2011 ;3(9):528-44.http://hdl.handle.net/20.500.12105/17966Basal-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.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Cell PolarityAdenocarcinomaAmino Acid OxidoreductasesBiomarkersBreast NeoplasmsFemaleHumansNeoplasm MetastasisLysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas.Attribution-NonCommercial-NoDerivatives 4.0 Internacional217325353952810.1002/emmm.2011001561757-4684EMBO molecular medicinehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377095/open access