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oai:repisalud.isciii.es:20.500.12105/179662024-11-29T16:06:11Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Moreno-Bueno, Gema author Salvador, Fernando author Martín, Alberto author Floristán, Alfredo author Cuevas, Eva P author Santos, Vanesa author Montes, Amalia author Morales, Saleta author Castilla, Maria Angeles author Rojo-Sebastián, Alejandro author Martínez, Alejandra author Hardisson, David author Csiszar, Katalin author Portillo, Francisco author Peinado, Héctor author Palacios, José author Cano, Amparo author 2011-09 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. EMBO Mol Med . 2011 ;3(9):528-44. 10.1002/emmm.201100156 1757-4684 EMBO molecular medicine https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377095/ 21732535 http://hdl.handle.net/20.500.12105/17966 Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas.