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Moreno-Bueno, G. et al.

Gema Moreno-Bueno, Fernando Salvador, Alberto Martín, Alfredo Floristán, Eva P. Cuevas, Vanesa Santos, Amalia Montes, Saleta Morales, Maria Angeles Castilla, Alejandro Rojo-Sebastián, Alejandra Martínez, David Hardisson, Katalin Csiszar, Francisco Portillo, Héctor Peinado, José Palacios, Amparo Cano,

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 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.[1]

References

Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas. Moreno-Bueno, G., Salvador, F., Martín, A., Floristán, A., Cuevas, E.P., Santos, V., Montes, A., Morales, S., Castilla, M.A., Rojo-Sebastián, A., Martínez, A., Hardisson, D., Csiszar, K., Portillo, F., Peinado, H., Palacios, J., Cano, A. EMBO. Mol. Med (2011) [Pubmed]

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