Journal
CELL CYCLE
Volume 11, Issue 21, Pages 3972-3982Publisher
LANDES BIOSCIENCE
DOI: 10.4161/cc.22227
Keywords
breast cancer; lactation; milk proteins; casein; STAT1; interferon signaling; cancer stem cells; metastasis
Categories
Funding
- Breast Cancer Alliance
- Margaret Q. Landenberger Research Foundation
- Breakthrough Breast Cancer in the U.K.
- European Research Council
Ask authors/readers for more resources
Here, we identified the milk protein alpha-casein as a novel suppressor of tumor growth and metastasis. Briefly, Met-1 mammary tumor cells expressing alpha-casein showed a similar to 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 alpha-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 alpha-casein would provide a more natural and non-toxic approach to the development of novel anticancer therapies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available