Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Cell cycle (Georgetown, Tex.), 2012-11, Vol.11 (21), p.3972-3982

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2012

Quelle

Taylor & Francis

Beschreibungen/Notizen

• 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.