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

التفاصيل البيبلوغرافية
العنوان: The milk protein α-casein functions as a tumor suppressor via activation of STAT1 signaling, effectively preventing breast cancer tumor growth and metastasis
المؤلفون: Diana Whitaker-Menezes, Jiao Xuanmao, Ubaldo E. Martinez-Outschoorn, Gloria Bonuccelli, Federica Sotgia, Zhao Lin, Anthony Howell, Franco Capozza, Aristotelis Tsirigos, Michael P. Lisanti, Remedios Castello-Cros
المصدر: Cell cycle (Georgetown, Tex.). 11(21)
سنة النشر: 2012
مصطلحات موضوعية: Apoptosis, Breast Neoplasms, Metastasis, Cell Line, Mice, Breast cancer, Downregulation and upregulation, Interferon, Cancer stem cell, Cell Movement, Report, medicine, Animals, Humans, Molecular Biology, Cell Proliferation, Mammary tumor, biology, Milk, Human, Gene Expression Profiling, CD44, Caseins, Cell Biology, medicine.disease, Up-Regulation, Gene expression profiling, Hyaluronan Receptors, STAT1 Transcription Factor, Cancer research, biology.protein, Neoplastic Stem Cells, Female, Interferons, Developmental Biology, medicine.drug, Signal Transduction
الوصف: 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.
تدمد: 1551-4005
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0030e6ef96a8aa31dc3f1755b2af5ed9
https://pubmed.ncbi.nlm.nih.gov/23047602
Rights: OPEN
رقم الانضمام: edsair.doi.dedup.....0030e6ef96a8aa31dc3f1755b2af5ed9
قاعدة البيانات: OpenAIRE