STAT5 confers lactogenic properties in breast tumorigenesis and restricts metastatic potential.

TitleSTAT5 confers lactogenic properties in breast tumorigenesis and restricts metastatic potential.
Publication TypeJournal Article
Year of Publication2022
AuthorsLin M, Ku AT, Dong J, Yue F, Jiang W, Ibrahim AAtef, Peng F, Creighton CJ, Nagi C, Gutierrez C, Rosen JM, Zhang XH-F, Hilsenbeck SG, Chen X, Du Y-CNancy, Huang S, Shi A, Fan Z, Li Y
JournalOncogene
Volume41
Issue48
Pagination5214-5222
Date Published2022 Nov
ISSN1476-5594
KeywordsAnimals, Breast, Breast Neoplasms, Cell Transformation, Neoplastic, Epithelial Cells, Female, Humans, Mammary Glands, Animal, Mice, STAT5 Transcription Factor
Abstract

Signal transducer and activator of transcription 5 (STAT5) promotes cell survival and instigates breast tumor formation, and in the normal breast it also drives alveolar differentiation and lactogenesis. However, whether STAT5 drives a differentiated phenotype in breast tumorigenesis and therefore impacts cancer spread and metastasis is unclear. We found in two genetically engineered mouse models of breast cancer that constitutively activated Stat5a (Stat5aca) caused precancerous mammary epithelial cells to become lactogenic and evolve into tumors with diminished potential to metastasize. We also showed that STAT5aca reduced the migratory and invasive ability of human breast cancer cell lines in vitro. Furthermore, we demonstrated that STAT5aca overexpression in human breast cancer cells lowered their metastatic burden in xenografted mice. Moreover, RPPA, Western blotting, and studies of ChIPseq data identified several EMT drivers regulated by STAT5. In addition, bioinformatic studies detected a correlation between STAT5 activity and better prognosis of breast cancer patients. Together, we conclude that STAT5 activation during mammary tumorigenesis specifies a tumor phenotype of lactogenic differentiation, suppresses EMT, and diminishes potential for subsequent metastasis.

DOI10.1038/s41388-022-02500-w
Alternate JournalOncogene
PubMed ID36261627
PubMed Central IDPMC9701164
Grant ListP30 CA125123 / CA / NCI NIH HHS / United States
S10 RR024574 / RR / NCRR NIH HHS / United States
R01 CA016303 / CA / NCI NIH HHS / United States
S10 OD028648 / OD / NIH HHS / United States
T32 CA203690 / CA / NCI NIH HHS / United States
P50 CA186784 / CA / NCI NIH HHS / United States
Related Faculty: 
Yi-Chieh (Nancy) Du, Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700