NF-[kappa]B non-cell-autonomously regulates cancer stem cell populations in the basal-like breast cancer subtype

Patients with triple-negative breast cancer display the highest rates of early relapse of all patients with breast cancer. The basal-like subtype, a subgroup of triple-negative breast cancer, exhibits high levels of constitutively active NF-κB signalling. Here we show that NF-κB activation, induced...

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Bibliographic Details
Published inNature communications Vol. 4; p. 2299
Main Authors Yamamoto, Mizuki, Taguchi, Yuu, Ito-kureha, Taku, Semba, Kentaro, Yamaguchi, Noritaka, Inoue, Jun-ichiro
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group 01.08.2013
Subjects
Biology
Breast cancer
Cytokines
Kinases
Medical prognosis
Phosphorylation
Stem cells
Japan
Okinawa
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Summary:Patients with triple-negative breast cancer display the highest rates of early relapse of all patients with breast cancer. The basal-like subtype, a subgroup of triple-negative breast cancer, exhibits high levels of constitutively active NF-κB signalling. Here we show that NF-κB activation, induced by inflammatory cytokines or by epigenetically dysregulated NIK expression, cell-autonomously upregulates JAG1 expression in non-cancer stem cells. This upregulation stimulates NOTCH signalling in cancer stem cells in trans, leading to an expansion of cancer stem cell populations. Among breast cancers, the NF-κB-dependent induction of JAG1 and the NOTCH-dependent expansion of the cancer stem cell population occur only in the basal-like subtype. Collectively, our results indicate that NF-κB has a non-cell-autonomous role in regulating cancer stem cell populations by forming intratumoural microenvironments composed of JAG1-expressing non-cancer stem cells with a basal-like subtype.
ISSN:2041-1723
DOI:10.1038/ncomms3299