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Title: Stratification and therapeutic potential of PML in metastatic breast cancer
Author: Martín-Martín, Natalia
Piva, Marco
Urosevic, Jelena
Aldaz, Paula
Sutherland, James David
Fernández-Ruiz, Sonia
Arreal, Leire
Torrano, Verónica
Cortazar, Ana Rosa
Planet, Evarist
Guiu, Marc
Radosevic Robin, Nina
Garcia, Stephane
Macías, Iratxe
Salvador, Fernando
Domenici, Giacomo
Rueda, Oscar M.
Zabala Letona, Amaia
Arruabarrena-Aristorena, Amaia
Zúñiga García, Patricia
Caro Maldonado, Alfredo
Valcarcel-Jimenez, Lorea
Sánchez Mosquera, Pilar
Varela Rey, Marta
Martínez Chantar, Maria Luz
Anguita, Juan
Ibrahim, Yasir H.
Scaltriti, Maurizio
Lawrie, Charles H.
Aransay, Ana Maria
Iovanna, Juan L.
Baselga, Jose
Caldas, Carlos
Barrio, Rosa
Serra, Violeta
Vivanco, Maria d. M.
Matheu, Ander
Gomis i Cabré, Roger
Carracedo, Arkaitz
Keywords: Càncer de mama
Interacció cel·lular
Breast cancer
Cell interaction
Issue Date: 24-Aug-2016
Publisher: Macmillan
Abstract: Patient stratification has been instrumental for the success of targeted therapies in breast cancer. However, the molecular basis of metastatic breast cancer and its therapeutic vulnerabilities remain poorly understood. Here we show that PML is a novel target in aggressive breast cancer. The acquisition of aggressiveness and metastatic features in breast tumours is accompanied by the elevated PML expression and enhanced sensitivity to its inhibition. Interestingly, we find that STAT3 is responsible, at least in part, for the transcriptional upregulation of PML in breast cancer. Moreover, PML targeting hampers breast cancer initiation and metastatic seeding. Mechanistically, this biological activity relies on the regulation of the stem cell gene SOX9 through interaction of PML with its promoter region. Altogether, we identify a novel pathway sustaining breast cancer aggressiveness that can be therapeutically exploited in combination with PML-based stratification.
Note: Reproducció del document publicat a:
It is part of: Nature Communications, 2016, vol. 7, p. 12595
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ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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