TY - JOUR
T1 - Slug/β-catenin-dependent proinflammatory phenotype in hypoxic breast cancer stem cells
AU - Storci, Gianluca
AU - Bertoni, Sara
AU - De Carolis, Sabrina
AU - Papi, Alessio
AU - Nati, Marina
AU - Ceccarelli, Claudio
AU - Pirazzini, Chiara
AU - Garagnani, Paolo
AU - Ferrarini, Alberto
AU - Buson, Genny
AU - Delledonne, Massimo
AU - Fiorentino, Michelangelo
AU - Capizzi, Elisa
AU - Gruppioni, Elisa
AU - Taffurelli, Mario
AU - Santini, Donatella
AU - Franceschi, Claudio
AU - Bandini, Giuseppe
AU - Bonifazi, Francesca
AU - Bonafé, Massimiliano
PY - 2013/11
Y1 - 2013/11
N2 - Cancer stem cell survival relies on the activation of inflammatory pathways, which is speculatively triggered by cell autonomous mechanisms or by microenvironmental stimuli. Here, we observed that hypoxic bone marrow stroma-derived transforming growth factor-β 1 promotes the growth of human breast cancer stem cells as mammospheres. The ensuing Slug-dependent serine 139 phosphorylation of the DNA damage sensor H2AX in breast cancer stem cells induces tumor necrosis factor-α and IL-8 mRNAs, whose stability is enhanced by cytoplasmic β-catenin. β-Catenin also up-regulates and binds miR-221, reducing the stability of the miR-221 targets Rad51 and ERα mRNAs. Our data show that the Slug/β-catenin-dependent activation of DNA damage signaling triggered by the hypoxic microenvironment sustains the proinflammatory phenotype of breast cancer stem cells.
AB - Cancer stem cell survival relies on the activation of inflammatory pathways, which is speculatively triggered by cell autonomous mechanisms or by microenvironmental stimuli. Here, we observed that hypoxic bone marrow stroma-derived transforming growth factor-β 1 promotes the growth of human breast cancer stem cells as mammospheres. The ensuing Slug-dependent serine 139 phosphorylation of the DNA damage sensor H2AX in breast cancer stem cells induces tumor necrosis factor-α and IL-8 mRNAs, whose stability is enhanced by cytoplasmic β-catenin. β-Catenin also up-regulates and binds miR-221, reducing the stability of the miR-221 targets Rad51 and ERα mRNAs. Our data show that the Slug/β-catenin-dependent activation of DNA damage signaling triggered by the hypoxic microenvironment sustains the proinflammatory phenotype of breast cancer stem cells.
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U2 - 10.1016/j.ajpath.2013.07.020
DO - 10.1016/j.ajpath.2013.07.020
M3 - Article
C2 - 24036252
AN - SCOPUS:84886703878
VL - 183
SP - 1688
EP - 1697
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 5
ER -