The milk protein α-casein functions as a tumor suppressor via activation of STAT1 signaling, effectively preventing breast cancer tumor growth and metastasis
Volume 11, Issue 21
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November 1, 2012
Pages 3972 - 3982http://dx.doi.org/10.4161/cc.22227
: STAT1, breast cancer, cancer stem cells, casein, interferon signaling, lactation, metastasis, milk proteins
Authors: Gloria Bonuccelli, Remedios Castello-Cros, Franco Capozza, Ubaldo E. Martinez-Outschoorn, Zhao Lin, Aristotelis Tsirigos, Jiao Xuanmao, Diana Whitaker-Menezes, Anthony Howell, Michael P. Lisanti and Federica Sotgia View affiliations
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.
Received: September 4, 2012; Accepted: September 13, 2012; Published Online: October 9, 2012
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