ArticleNature cell biology2014
Stat3 controls cell death during mammary gland involution by regulating uptake of milk fat globules and lysosomal membrane permeabilization.
Article in Nature cell biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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Who cites it
100 citing papers in PubMed, 167 citations in OpenAlex.
- Pregnancy-induced tissue-resident memory-like T cells contribute to tumor control in breast cancer.Nature immunology · 2026Article
- SOX9 and SEMA7A regulate cell plasticity in the postpartum mammary gland with implications for breast cancer.bioRxiv : the preprint server for biology · 2026Article
- Induction of senescence during postpartum mammary gland involution supports tissue remodeling and promotes postpartum tumorigenesis.Nature aging · 2026Article
- Out of Nucleus: Serine 727 Phosphorylation Orchestrates Non-Canonical STAT3 Functions-Relevance to Triple-Negative Breast Cancer.International journal of molecular sciences · 2026Review
- Estrogen Signaling During Abrupt Involution and Long-Term Metabolic Signature Similar to Estrogen Receptor-Negative Breast Cancer.International journal of molecular sciences · 2026Article
- Article
- Molecular Regulatory Mechanisms of Mammary Gland Development: A Review.Animals : an open access journal from MDPI · 2025Review
- Cathepsin L as a dual-target to mitigate muscle wasting while enhancing anti-tumor efficacy of anti-PD-L1.Nature communications · 2025Article
- Little women: the relevance and reliance on mouse models for mammary gland research and next steps for translation.Journal of mammary gland biology and neoplasia · 2025Review
- Reproductive state controls transcription in the murine liver, with implications for breast cancer liver metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ATR Deficiency Impairs DNA Damage Repair and Accelerates Cellular Senescence in Bovine Mammary Epithelial Cells, Leading to Lactation Dysfunction.Animals : an open access journal from MDPI · 2025Article
- Understanding Susceptibility to Breast Cancer: From Risk Factors to Prevention Strategies.International journal of molecular sciences · 2025Review
- From Embryogenesis to Senescence: The Role of Mammary Gland Physiology in Breast Cancer Risk.Cancers · 2025Review
- Review
- Divergent paths of mammary gland involution: unveiling the cellular dynamics in abruptly and gradually involuted mouse models.Breast cancer research : BCR · 2025Article
- Relationship between breast tissue involution and breast cancer.Frontiers in oncology · 2025Review
- Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome.Cell genomics · 2024Article
- Autophagy-lysosomal-associated neuronal death in neurodegenerative disease.Acta neuropathologica · 2024Review
- Immune Cell Contribution to Mammary Gland Development.Journal of mammary gland biology and neoplasia · 2024Review
- Methods for investigating STAT3 regulation of lysosomal function in mammary epithelial cells.Journal of mammary gland biology and neoplasia · 2024Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
We have previously demonstrated that Stat3 regulates lysosomal-mediated programmed cell death (LM-PCD) during mouse mammary gland involution in vivo. However, the mechanism that controls the release of lysosomal cathepsins to initiate cell death in this context has not been elucidated. We show here that Stat3 regulates the formation of large lysosomal vacuoles that contain triglyceride. Furthermore, we demonstrate that milk fat globules (MFGs) are toxic to epithelial cells and that, when applied to purified lysosomes, the MFG hydrolysate oleic acid potently induces lysosomal leakiness. Additionally, uptake of secreted MFGs coated in butyrophilin 1A1 is diminished in Stat3-ablated mammary glands and loss of the phagocytosis bridging molecule MFG-E8 results in reduced leakage of cathepsins in vivo. We propose that Stat3 regulates LM-PCD in mouse mammary gland by switching cellular function from secretion to uptake of MFGs. Thereafter, perturbation of lysosomal vesicle membranes by high levels of free fatty acids results in controlled leakage of cathepsins culminating in cell death.
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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.