期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 225, 期 3, 页码 682-691出版社
WILEY-BLACKWELL
DOI: 10.1002/jcp.22264
关键词
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资金
- PRIN [KTRN38]
- Cornelia Pallotti and Roberto Pallotti Foundation
- FIRB Project [RBNE03KZRJ]
- MAIN FPVI EU network of excellence
- USA NIH [GM066882]
- Fondazione Cassa di Risparmio in Bologna and Fondazione Banca del Monte e Ravenna
Extracellular and intracellular mediators of inflammation, such as tumor necrosis factor alpha (TNF alpha) and NF-kappaB (NF-kappa B), play major roles in breast cancer pathogenesis, progression and relapse. SLUG, a mediator of the epithelial mesenchymal transition process, is over-expressed in CD44(-)/CD24(-) tumor initiating breast cancer cells and in basal-like carcinoma, a subtype of aggressive breast cancer endowed with a stem cell-like gene expression profile. Cancer stem cells also over-express members of the pro-inflammatory NF-kappa B network, but their functional relationship with SLUG expression in breast cancer cells remains unclear. Here, we show that TNF alpha treatment of human breast cancer cells up-regulates SLUG with a dependency on canonical NF-kappa B/HIF1 alpha signaling, which is strongly enhanced by p53 inactivation. Moreover, SLUG up-regulation engenders breast cancer cells with stem cell-like properties including enhanced expression of CD44 and Jagged-1 in conjunction with estrogen receptor alpha down-regulation, growth as mammospheres, and extracellular matrix invasiveness. Our results reveal a molecular mechanism whereby TNF alpha, a major pro-inflammatory cytokine, imparts breast cancer cells with stem cell-like features, which are connected to increased tumor aggressiveness. J. Cell. Physiol. 225: 682-691, 2010. (C) 2010 Wiley-Liss, Inc.
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