TY - JOUR
T1 - Stratification and therapeutic potential of PML in metastatic breast cancer
AU - Martín-Martín, Natalia
AU - Piva, Marco
AU - Urosevic, Jelena
AU - Aldaz, Paula
AU - Sutherland, James D.
AU - Fernández-Ruiz, Sonia
AU - Arreal, Leire
AU - Torrano, Verónica
AU - Cortazar, Ana R.
AU - Planet, Evarist
AU - Guiu, Marc
AU - Radosevic-Robin, Nina
AU - Garcia, Stephane
AU - Macías, Iratxe
AU - Salvador, Fernando
AU - Domenici, Giacomo
AU - Rueda, Oscar M.
AU - Zabala-Letona, Amaia
AU - Arruabarrena-Aristorena, Amaia
AU - Zúñiga-García, Patricia
AU - Caro-Maldonado, Alfredo
AU - Valcárcel-Jiménez, Lorea
AU - Sánchez-Mosquera, Pilar
AU - Varela-Rey, Marta
AU - Martínez-Chantar, Maria Luz
AU - Anguita, Juan
AU - Ibrahim, Yasir H.
AU - Scaltriti, Maurizio
AU - Lawrie, Charles H.
AU - Aransay, Ana M.
AU - Iovanna, Juan L.
AU - Baselga, Jose
AU - Caldas, Carlos
AU - Barrio, Rosa
AU - Serra, Violeta
AU - Dm Vivanco, Maria
AU - Matheu, Ander
AU - Gomis, Roger R.
AU - Carracedo, Arkaitz
N1 - Publisher Copyright:
© The Author(s) 2016.
PY - 2016/8/24
Y1 - 2016/8/24
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84984699037
U2 - 10.1038/ncomms12595
DO - 10.1038/ncomms12595
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C2 - 27553708
AN - SCOPUS:84984699037
SN - 2041-1723
VL - 7
JO - Nature Communications
JF - Nature Communications
M1 - 12595
ER -
SDG 3 Good Health and Well-being