• Open Access

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

Authors

  • Gema Moreno-Bueno,

    Corresponding author
    1. Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain
    2. MD Anderson Cancer Center Madrid, Spain
    • Gema Moreno-Bueno, Tel: +34 91 4976798; Fax: +34 91 5854401

      Amparo Cano, Tel: +34 91 4975400; Fax: +34 91 5854401

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  • Fernando Salvador,

    1. Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain
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  • Alberto Martín,

    1. Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain
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  • Alfredo Floristán,

    1. Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain
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  • Eva P. Cuevas,

    1. Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain
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  • Vanesa Santos,

    1. Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain
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  • Amalia Montes,

    1. Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain
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  • Saleta Morales,

    1. Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain
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  • Maria Angeles Castilla,

    1. Unidad de Gestión Clínica de Anatomía Patológica and Grupo de Patología Molecular del Cáncer, Hospital Virgen del Rocío-IBIS, Instituto Biosanitario de Sevilla, Sevilla, Spain
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  • Alejandro Rojo-Sebastián,

    1. MD Anderson Cancer Center Madrid, Spain
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  • Alejandra Martínez,

    1. Departamento de Anatomía Patológica. Hospital La Paz-IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain
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  • David Hardisson,

    1. Departamento de Anatomía Patológica. Hospital La Paz-IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain
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  • Katalin Csiszar,

    1. John A Burns School of Medicine, University of Hawaii, Honolulu, HI, USA
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  • Francisco Portillo,

    1. Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain
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  • Héctor Peinado,

    1. Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain
    2. Departments of Pediatrics, Weill Medical College of Cornell University, 515E 71st Street, New York 10021, USA
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  • José Palacios,

    1. Unidad de Gestión Clínica de Anatomía Patológica and Grupo de Patología Molecular del Cáncer, Hospital Virgen del Rocío-IBIS, Instituto Biosanitario de Sevilla, Sevilla, Spain
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  • Amparo Cano

    Corresponding author
    1. Departamento de Bioquímica, UAM, Instituto de Investigaciones Biomédicas “Alberto Sols”, CSIC-UAM, IdiPAZ, Instituto de Investigación Sanitaria La Paz, Madrid, Spain
    • Gema Moreno-Bueno, Tel: +34 91 4976798; Fax: +34 91 5854401

      Amparo Cano, Tel: +34 91 4975400; Fax: +34 91 5854401

    Search for more papers by this author

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.

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