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...

Full description

Saved in:
Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Vol. 11; no. 21; pp. 3972 - 3982
Main Authors: 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
Format: Journal Article
Language:English
Published: United States Taylor & Francis 01.11.2012
Landes Bioscience
Subjects:
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
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
Bibliography: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