ArticleCell death and differentiation2014
Dysregulated STAT1-SOCS1 control of JAK2 promotes mammary luminal progenitor cell survival and drives ERα(+) tumorigenesis.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Review
- Th1 Cytokines Inhibit Acinar Morphogenesis and Milk Protein Expression in 3D Mammary Cultures.Biomedicines · 2025Article
- High CTLA-4 gene expression is an independent good prognosis factor in breast cancer patients, especially in the HER2-enriched subtype.Cancer cell international · 2024Article
- Wee1 inhibitor PD0166285 sensitized TP53 mutant lung squamous cell carcinoma to cisplatin via STAT1.Cancer cell international · 2024Article
- Functional CRISPR screens in T cells reveal new opportunities for cancer immunotherapies.Molecular cancer · 2024Review
- Advances in Immunocompetent Mouse and Rat Models.Cold Spring Harbor perspectives in medicine · 2024Review
- STAT family of transcription factors in breast cancer: Pathogenesis and therapeutic opportunities and challenges.Seminars in cancer biology · 2022Review
- Ductal Carcinoma in Situ: Molecular Changes Accompanying Disease Progression.Journal of mammary gland biology and neoplasia · 2022Review
- Advances in Rodent Models for Breast Cancer Formation, Progression, and Therapeutic Testing.Frontiers in oncology · 2021Review
- Intraductal Injection of Lentivirus Vectors for Stably Introducing Genes into Rat Mammary Epithelial Cells in Vivo.Journal of mammary gland biology and neoplasia · 2020Article
- Signal transducer and activator of transcription (STAT) 1 and STAT3 are expressed in the human ovary and have Janus kinase 1-independent functions in the COV434 human granulosa cell line.Reproduction, fertility, and development · 2020Article
- Prognostic value of key genes of the JAK-STAT signaling pathway in patients with cutaneous melanoma.Oncology letters · 2020Article
- Rationale and Roadmap for Developing Panels of Hotspot Cancer Driver Gene Mutations as Biomarkers of Cancer Risk.Environmental and molecular mutagenesis · 2020Review
- Article
- Demethylation of SOCS1 mediates its abnormally high expression in ovarian cancer.Oncology letters · 2019Article
- Progesterone Receptor Attenuates STAT1-Mediated IFN Signaling in Breast Cancer.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer.International journal of molecular sciences · 2018Review
- Mammary Stem Cells and Breast Cancer Stem Cells: Molecular Connections and Clinical Implications.Biomedicines · 2018Review
- "Do We Know Jack" About JAK? A Closer Look at JAK/STAT Signaling Pathway.Frontiers in oncology · 2018Review
- Aging Mouse Models Reveal Complex Tumor-Microenvironment Interactions in Cancer Progression.Frontiers in cell and developmental biology · 2018Review
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14 authors at 3 institutions in 4 countries.
Funding
Abstract
We previously reported that STAT1 expression is frequently abrogated in human estrogen receptor-α-positive (ERα(+)) breast cancers and mice lacking STAT1 spontaneously develop ERα(+) mammary tumors. However, the precise mechanism by which STAT1 suppresses mammary gland tumorigenesis has not been fully elucidated. Here we show that STAT1-deficient mammary epithelial cells (MECs) display persistent prolactin receptor (PrlR) signaling, resulting in activation of JAK2, STAT3 and STAT5A/5B, expansion of CD61(+) luminal progenitor cells and development of ERα(+) mammary tumors. A failure to upregulate SOCS1, a STAT1-induced inhibitor of JAK2, leads to unopposed oncogenic PrlR signaling in STAT1(-/-) MECs. Prophylactic use of a pharmacological JAK2 inhibitor restrains the proportion of luminal progenitors and prevents disease induction. Systemic inhibition of activated JAK2 induces tumor cell death and produces therapeutic regression of pre-existing endocrine-sensitive and refractory mammary tumors. Thus, STAT1 suppresses tumor formation in mammary glands by preventing the natural developmental function of a growth factor signaling pathway from becoming pro-oncogenic. In addition, targeted inhibition of JAK2 may have significant therapeutic potential in controlling ERα(+) breast cancer in humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.