Pentraxin-3 is a PI3K signaling target that promotes stem cell-like traits in basal-like breast cancers.

Autor:	Thomas C; Department of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA., Henry W; Department of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA., Cuiffo BG; Department of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA., Collmann AY; Department of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA., Marangoni E; Institut Curie, Paris Cedex 05, France., Benhamo V; Institut Curie, Paris Cedex 05, France., Bhasin MK; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA., Fan C; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Fuhrmann L; Institut Curie, Paris Cedex 05, France., Baldwin AS; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Perou C; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Vincent-Salomon A; Institut Curie, Paris Cedex 05, France., Toker A; Department of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA., Karnoub AE; Department of Pathology and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. akarnoub@bidmc.harvard.edu.; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA.
Jazyk:	angličtina
Zdroj:	Science signaling [Sci Signal] 2017 Feb 21; Vol. 10 (467). Date of Electronic Publication: 2017 Feb 21.
DOI:	10.1126/scisignal.aah4674
Abstrakt:	Basal-like breast cancers (BLBCs) exhibit hyperactivation of the phosphoinositide 3-kinase (PI3K) signaling pathway because of the frequent mutational activation of the PIK3CA catalytic subunit and the genetic loss of its negative regulators PTEN (phosphatase and tensin homolog) and INPP4B (inositol polyphosphate-4-phosphatase type II). However, PI3K inhibitors have had limited clinical efficacy in BLBC management because of compensatory amplification of PI3K downstream signaling loops. Therefore, identification of critical PI3K mediators is paramount to the development of effective BLBC therapeutics. Using transcriptomic analysis of activated PIK3CA-expressing BLBC cells, we identified the gene encoding the humoral pattern recognition molecule pentraxin-3 (PTX3) as a critical target of oncogenic PI3K signaling. We found that PTX3 abundance is stimulated, in part, through AKT- and nuclear factor κB (NF-κB)-dependent pathways and that presence of PTX3 is necessary for PI3K-induced stem cell-like traits. We further showed that PTX3 expression is greater in tumor samples from patients with BLBC and that it is prognostic of poor patient survival. Our results thus reveal PTX3 as a newly identified PI3K-regulated biomarker and a potential therapeutic target in BLBC. (Copyright © 2017, American Association for the Advancement of Science.)
Databáze:	MEDLINE
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