The milk protein α-casein functions as a tumor suppressor via activation of STAT1 signaling, effectively preventing breast cancer tumor growth and metastasis

Here, we identified the milk protein α-casein as a novel suppressor of tumor growth and metastasis. Briefly, Met-1 mammary tumor cells expressing α-casein showed a ~5-fold reduction in tumor growth and a near 10-fold decrease in experimental metastasis. To identify the molecular mechanism(s), we per...

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Vydané v:	Cell cycle (Georgetown, Tex.) Ročník 11; číslo 21; s. 3972 - 3982
Hlavní autori:	Bonuccelli, Gloria, Castello-Cros, Remedios, Capozza, Franco, Martinez-Outschoorn, Ubaldo E., Lin, Zhao, Tsirigos, Aristotelis, Xuanmao, Jiao, Whitaker-Menezes, Diana, Howell, Anthony, Lisanti, Michael P., Sotgia, Federica
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Taylor & Francis 01.11.2012 Landes Bioscience
Predmet:	Animals Apoptosis - drug effects Binding Biology Bioscience breast cancer Breast Neoplasms - metabolism Breast Neoplasms - pathology Breast Neoplasms - prevention & control Calcium Cancer cancer stem cells casein Caseins - metabolism Caseins - pharmacology Cell Cell Line Cell Movement - drug effects Cell Proliferation - drug effects Cycle Female Gene Expression Profiling Humans Hyaluronan Receptors - metabolism interferon signaling Interferons - metabolism lactation Landes metastasis Mice milk proteins Milk, Human Neoplastic Stem Cells - metabolism Organogenesis Proteins Signal Transduction - drug effects STAT1 STAT1 Transcription Factor - genetics STAT1 Transcription Factor - metabolism Up-Regulation
ISSN:	1538-4101, 1551-4005, 1551-4005
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Shrnutí:	Here, we identified the milk protein α-casein as a novel suppressor of tumor growth and metastasis. Briefly, Met-1 mammary tumor cells expressing α-casein showed a ~5-fold reduction in tumor growth and a near 10-fold decrease in experimental metastasis. To identify the molecular mechanism(s), we performed genome-wide transcriptional profiling. Interestingly, our results show that α-casein upregulates gene transcripts associated with interferon/STAT1 signaling and downregulates genes associated with "stemness." These findings were validated by immunoblot and FACS analysis, which showed the upregulation and hyperactivation of STAT1 and a decrease in the number of CD44(+) "cancer stem cells." These gene signatures were also able to predict clinical outcome in human breast cancer patients. Thus, we conclude that a lactation-based therapeutic strategy using recombinant α-casein would provide a more natural and non-toxic approach to the development of novel anticancer therapies.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current affiliation: Breakthrough Breast Cancer Research Unit; University of Manchester; Manchester, UK
ISSN:	1538-4101 1551-4005 1551-4005
DOI:	10.4161/cc.22227