Stat3 controls cell death during mammary gland involution by regulating uptake of milk fat globules and lysosomal membrane permeabilization
Open accessAbstract
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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STAT3 promotes lysosome-dependent cell death during mammary gland involution post-lactation by upregulating CTSB and CTSL and downregulating SPI2A.
“Moreover, STAT3 reportedly promotes lysosome-dependent cell death during the involution of mammary gland post-lactation as it upregulates the expression of cathepsin B (CTSB) and CTSL, while downregulating their endogenous inhibitor serine (or cysteine) peptidase inhibitor, clade A, member 3G (SERPINA3G; best known as SPI2A) [774, 775].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [775]
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1 retracted
Kitambi, S. S., Toledo, E. M., Usoskin, D., Wee, S., Harisankar, A., Svensson, R., Sigmundsson, K., Kalderén, C., Niklasson, M., Kundu, S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.02.021 · Cited by 98 · see citing works
RetractedGuidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996 · see citing works
Autophagy regulates lipid metabolism
Singh, R., Kaushik, S., Wang, Y., Xiang, Y., Novak, I., Komatsu, M., Tanaka, K., Cuervo, A. M., & Czaja, M. J. (2009) · Nature · doi:10.1038/nature07976 · Cited by 3,975 · see citing works
Triglyceride accumulation protects against fatty acid-induced lipotoxicity
Listenberger, L. L., Han, X., Lewis, S. E., Cases, S., Farese, R. V., Ory, D. S., & Schaffer, J. E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0630588100 · Cited by 2,075 · see citing works
Lysosomes: fusion and function
Luzio, J. P., Pryor, P. R., & Bright, N. A. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2217 · Cited by 1,737 · see citing works
During autophagy mitochondria elongate, are spared from degradation and sustain cell viability
Gomes, L. C., Benedetto, G. D., & Scorrano, L. (2011) · Nature Cell Biology · doi:10.1038/ncb2220 · Cited by 1,735 · see citing works
Lysosomes and autophagy in cell death control
Kroemer, G., & Jäättelä, M. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1738 · Cited by 1,291 · see citing works
Lysosomal cell death at a glance
Aits, S., & Jäättelä, M. (2013) · Journal of Cell Science · doi:10.1242/jcs.091181 · Cited by 667 · see citing works
Foghsgaard, L., Wissing, D., Mauch, D., Lademann, U. A., Bastholm, L., Boes, M. L., Elling, F., Leist, M., & Jäättelä, M. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.153.5.999 · Cited by 629 · see citing works
Morphological classification of plant cell deaths
van Doorn, W. G., Beers, E. P., Dangl, J. L., Franklin-Tong, V. E., Gallois, P., Hara-Nishimura, I., Jones, A. M., Kawai-Yamada, M., Lam, E., Mundy, J., et al. (2011) · Cell Death & Differentiation · doi:10.1038/cdd.2011.36 · Cited by 584 · see citing works
Lund, L. R., Rømer, J., Thomasset, N., Solberg, H., Pyke, C., Bissell, M. J., Danø, K., & Werb, Z. (1996) · Development · doi:10.1242/dev.122.1.181 · Cited by 547 · see citing works
Chapman, R. S., Lourenco, P. C., Tonner, E., Flint, D. J., Selbert, S., Takeda, K., Akira, S., Clarke, A. R., & Watson, C. J. (1999) · Genes & Development · doi:10.1101/gad.13.19.2604 · Cited by 480 · see citing works
Self-citationMammary development in the embryo and adult: a journey of morphogenesis and commitment
Watson, C. J., & Khaled, W. T. (2008) · Development · doi:10.1242/dev.005439 · Cited by 414 · see citing works
Self-citationLysosomal involvement in cell death and cancer
Kirkegaard, T., & Jäättelä, M. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2008.09.008 · Cited by 395 · see citing works
Origin and Secretion of Milk Lipids
Mather, I. H., & Keenan, T. W. (1998) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1023/a:1018711410270 · Cited by 361 · see citing works
Clarkson, R. W. E., Wayland, M. T., Lee, J., Freeman, T. C., & Watson, C. J. (2003) · Breast Cancer Research · doi:10.1186/bcr754 · Cited by 329 · see citing works
Self-citationAlonzi, T., Maritano, D., Gorgoni, B., Rizzuto, G., Libert, C., & Poli, V. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.5.1621-1632.2001 · Cited by 329 · see citing works
Lactadherin promotes VEGF-dependent neovascularization
Silvestre, J., Théry, C., Hamard, G., Boddaert, J., Aguilar, B. A., Delcayre, A. X., Houbron, C., Tamarat, R., Blanc‐Brude, O., Heeneman, S., et al. (2005) · Nature Medicine · doi:10.1038/nm1233 · Cited by 320 · see citing works
Stat3 controls lysosomal-mediated cell death in vivo
Kreuzaler, P. A., Staniszewska, A. D., Li, W., Omidvar, N., Kedjouar, B., Turkson, J., Poli, V., Flavell, R. A., Clarkson, R. W. E., & Watson, C. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2171 · Cited by 312 · see citing works
Self-citationRoth, W., Deussing, J. M., Botchkarev, V. A., Pauly-Evers, M., Säftig, P., Hafner, A., Schmidt, P. M., Schmahl, W. W., Scherer, J., Anton‐Lamprecht, I., et al. (2000) · The FASEB Journal · doi:10.1096/fj.99-0970com · Cited by 308 · see citing works
Cancer-associated lysosomal changes: friends or foes?
Kallunki, T., Olsen, O. D., & Jäättelä, M. (2012) · Oncogene · doi:10.1038/onc.2012.292 · Cited by 301 · see citing works
Deletion of cells by apoptosis during castration-induced involution of the rat prostate
Kerr, J. F. R., & Searle, J. W. (1973) · Virchows Archiv B Cell Pathology Including Molecular Pathology · doi:10.1007/bf02889300 · Cited by 289 · see citing works
Programmed cell death in Dictyostelium
Cornillon, S., Foa, C., Davoust, J. M., Buonavista, N., Gross, J. D., & Golstein, P. (1994) · Journal of Cell Science · doi:10.1242/jcs.107.10.2691 · Cited by 287 · see citing works
Yuzefovych, L., Wilson, G., & Rachek, L. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00238.2010 · Cited by 280 · see citing works
Caspase-independent cell death?
Lockshin, R. A., & Zakeri, Z. F. (2004) · Oncogene · doi:10.1038/sj.onc.1207514 · Cited by 270 · see citing works
Watson, C. J. (2006) · Breast Cancer Research · doi:10.1186/bcr1401 · Cited by 268 · see citing works
Self-citationThe role of vacuole in plant cell death
Hara‐Nishimura, I., & Hatsugai, N. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.70 · Cited by 257 · see citing works
Maltese, W. A., & Overmeyer, J. H. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.02.028 · Cited by 254 · see citing works
Organelle-specific initiation of cell death
Galluzzi, L., Bravo-San Pedro, J. M., & Kroemer, G. (2014) · Nature Cell Biology · doi:10.1038/ncb3005 · Cited by 239 · see citing works
The cellular pathology of lysosomal diseases
Cox, T. M., & Cachón-González, M. B. (2011) · The Journal of Pathology · doi:10.1002/path.3021 · Cited by 222 · see citing works
Ogg, S. L., Weldon, A. K., Dobbie, L., Smith, A. J. H., & Mather, I. H. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402930101 · Cited by 212 · see citing works
Targeting the tumor microenvironment
Bournazou, E., & Bromberg, J. (2013) · JAK-STAT · doi:10.4161/jkst.23828 · Cited by 191 · see citing works
Ono, K., Kim, S. O., & Han, J. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.2.665-676.2003 · Cited by 182 · see citing works
Ernst Reichmann, A., Ball, R., Groner, B., & Friis, R. R. (1989) · The Journal of Cell Biology · doi:10.1083/jcb.108.3.1127 · Cited by 178 · see citing works
Lockshin, R. A., & Williams, C. M. (1965) · Journal of Insect Physiology · doi:10.1016/0022-1910(65)90186-1 · Cited by 176 · see citing works
Remodeling mechanisms of the mammary gland during involution
Watson, C. J., & Kreuzaler, P. A. (2011) · The International Journal of Developmental Biology · doi:10.1387/ijdb.113414cw · Cited by 166 · see citing works
Self-citationKilling a cancer: what are the alternatives?
Kreuzaler, P. A., & Watson, C. J. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3264 · Cited by 162 · see citing works
Self-citationMonks, J., Smith-Steinhart, C., Kruk, E. R., Fadok, V. A., & Henson, P. M. (2007) · Biology of Reproduction · doi:10.1095/biolreprod.107.065045 · Cited by 158 · see citing works
Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8
Hanayama, R., & Nagata, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508599102 · Cited by 133 · see citing works
Humphreys, R. C., Bierie, B., Zhao, L., Raz, R., Levy, D. E., & Hennighausen, L. G. (2002) · Endocrinology · doi:10.1210/en.2002-220224 · Cited by 130 · see citing works
BAMLET Activates a Lysosomal Cell Death Program in Cancer Cells
Rammer, P., Groth‐Pedersen, L., Kirkegaard, T., Daugaard, M., Rytter, A., Szyniarowski, P., Høyer-Hansen, M. H., Povlsen, L. K., Nylandsted, J., Larsen, J. E., et al. (2010) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0559 · Cited by 127 · see citing works
Hughes, K., Wickenden, J. A., Allen, J. E., & Watson, C. J. (2011) · The Journal of Pathology · doi:10.1002/path.3961 · Cited by 125 · see citing works
Self-citationLysosomal membrane permeabilization during apoptosis ‐ involvement of Bax?
Kågedal, K., Johansson, A., Johansson, U., Heimlich, G., Roberg, K. B., Wang, N. S., Jürgensmeier, J. M., & Öllinger, K. M. (2005) · International Journal of Experimental Pathology · doi:10.1111/j.0959-9673.2005.00442.x · Cited by 124 · see citing works
Vasiljeva, O. S., Korovin, M. S., Gajda, M. R., Brodoefel, H., Bojić, L., Krüger, A., Schurigt, U., Sevenich, L., Turk, B., Peters, C., et al. (2008) · Oncogene · doi:10.1038/onc.2008.59 · Cited by 115 · see citing works
Quantitative gas-liquid chromatographic analysis of rodent milk triglycerides
Smith, S., Watts, R., & Dils, R. (1968) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)43142-6 · Cited by 109 · see citing works
Mfge8 Is Critical for Mammary Gland Remodeling during Involution
Atabai, K., Fernandez, R. J., Huang, X., Ueki, I. F., Kline, A., Li, Y., Sadatmansoori, S., Smith-Steinhart, C., Zhu, W., Pytela, R., et al. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-02-0128 · Cited by 107 · see citing works
Efficient BLG-Cre Mediated Gene Deletion in the Mammary Gland
Selbert, S., & Bentley, D. J. (1998) · Transgenic Research · doi:10.1023/a:1008848304391 · Cited by 99 · see citing works
The biological activities of protein/oleic acid complexes reside in the fatty acid
Fontana, A., Spolaore, B., & de Laureto, P. P. (2013) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2013.02.041 · Cited by 91 · see citing works
Manzoni, C., & Lewis, P. A. (2013) · The FASEB Journal · doi:10.1096/fj.12-223842 · Cited by 62 · see citing works
Cell-free fusion of bacteria-containing phagosomes with endocytic compartments
Becken, U., Jeschke, A., Veltman, K., & Haas, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007295107 · Cited by 52 · see citing works
Jespersen, H., Andersen, J. A., Ditzel, H. J., & Mouritsen, O. G. (2011) · Biochimie · doi:10.1016/j.biochi.2011.07.029 · Cited by 46 · see citing works
Huai, J., Vögtle, F.-N., Jöckel, L., Li, Y., Kiefer, T., Ricci, J.-E., & Borner, C. (2013) · Journal of Cell Science · doi:10.1242/jcs.129999 · Cited by 43 · see citing works
A Test of Current Models for the Mechanism of Milk‐Lipid Droplet Secretion
Jeong, J., Lisinski, I., Kadegowda, A. K. G., Shin, H., Wooding, F. B. P., Daniels, B. R., Schaack, J. B., & Mather, I. H. (2013) · Traffic · doi:10.1111/tra.12087 · Cited by 36 · see citing works
Zaragozá, R., Torres, L., Garcı́a, C., Eroles, P., Corrales, F. J., Bosch, A., Lluch, A. M., García–Trevijano, E. R., & Vinã, J. R. (2009) · Biochemical Journal · doi:10.1042/bj20081746 · Cited by 32 · see citing works
Helminen, H. J., & Ericsson, J. L. E. (1971) · Experimental Cell Research · doi:10.1016/0014-4827(71)90167-4 · Cited by 31 · see citing works
New insights into cathepsin D in mammary tissue development and remodeling
Margaryan, N. V., Kirschmann, D. A., Lipavsky, A., Bailey, C. M., Hendrix, M. J. C., & Khalkhali‐Ellis, Z. (2010) · Cancer Biology & Therapy · doi:10.4161/cbt.10.5.12534 · Cited by 29 · see citing works
Jahreiss, L., Renna, M., Bittman, R., Arthur, G., & Rubinsztein, D. C. (2009) · Autophagy · doi:10.4161/auto.9120 · Cited by 29 · see citing works
Unger, R. H., Scherer, P. E., & Holland, W. L. (2013) · Molecular Biology of the Cell · doi:10.1091/mbc.e12-10-0774 · Cited by 27 · see citing works
Lysosomal Acid Lipase: Assay and Purification
Merkel, M., Tilkorn, A.-C., Greten, H., & Ameis, D. (2003) · Humana Press eBooks · doi:10.1385/1-59259-581-2:95 · Cited by 17 · see citing works
Necrotic cell death: harnessing the Dark side of the Force in mammary gland involution
Luke, C. J., & Silverman, G. A. (2011) · Nature Cell Biology · doi:10.1038/ncb0311-197 · Cited by 10 · see citing works
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Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Lysosomal membrane permeabilization and cell death
Wang, F., Gómez‐Sintes, R., & Boya, P. (2018) · Traffic · doi:10.1111/tra.12613 · Cited by 781 · see citing works
Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response
Olson, O. C., & Joyce, J. A. (2015) · Nature reviews. Cancer · doi:10.1038/nrc4027 · Cited by 703 · see citing works
Therapeutically exploiting STAT3 activity in cancer — using tissue repair as a road map
Huynh, J., Chand, A. L., Gough, D. J., & Ernst, M. (2018) · Nature reviews. Cancer · doi:10.1038/s41568-018-0090-8 · Cited by 507 · see citing works
Sensitive detection of lysosomal membrane permeabilization by lysosomal galectin puncta assay
Aits, S., Kricker, J. A., Liu, B., Ellegaard, A., Hämälistö, S., Tvingsholm, S. A., Corcelle–Termeau, E., Høgh, S., Farkas, T., Jonassen, A. H., et al. (2015) · Autophagy · doi:10.1080/15548627.2015.1063871 · Cited by 439 · see citing works
Emerging roles for lipids in non-apoptotic cell death
Magtanong, L., Ko, P., & Dixon, S. J. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.25 · Cited by 259 · see citing works
Ferroptosis is a lysosomal cell death process
Gao, H., Bai, Y., Jia, Y., Zhao, Y., Kang, R., Tang, D., & Dai, E. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.07.078 · Cited by 249 · see citing works
Hormonal regulation of mammary gland development and lactation
Hannan, F. M., Elajnaf, T., Vandenberg, L. N., Kennedy, S., & Thakker, R. V. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00742-y · Cited by 242 · see citing works
Lysosomal cell death mechanisms in aging
Gómez-Sintes, R., Ledesma, M. D., & Boya, P. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.02.009 · Cited by 216 · see citing works
Serrano‐Puebla, A., & Boya, P. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12966 · Cited by 204 · see citing works
The role of lysosomes in metabolic and autoimmune diseases
Gros, F., & Muller, S. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00692-2 · Cited by 199 · see citing works
Challenges in carrier‐mediated intracellular delivery: moving beyond endosomal barriers
Stewart, M. P., Lorenz, A. S., Dahlman, J. E., & Sahay, G. (2015) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1377 · Cited by 154 · see citing works
Regulation of Immunity by Butyrophilins
Rhodes, D. A., Reith, W., & Trowsdale, J. (2016) · Annual Review of Immunology · doi:10.1146/annurev-immunol-041015-055435 · Cited by 155 · see citing works
Mahamed, D., Boullé, M., Ganga, Y., Arthur, C. M., Skroch, S., Lance, O., Catinas, O., Pillay, K., Naicker, M., Rampersad, S., et al. (2017) · eLife · doi:10.7554/elife.22028 · Cited by 145 · see citing works
How Lysosomes Sense, Integrate, and Cope with Stress
Säftig, P., & Puertollano, R. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.09.004 · Cited by 136 · see citing works
Mechanisms of Regulated Cell Death: Current Perspectives
Santagostino, S. F., Assenmacher, C., Tarrant, J. C., Adedeji, A. O., & Radaelli, E. (2021) · Veterinary Pathology · doi:10.1177/03009858211005537 · Cited by 133 · see citing works
Lysosomes in cancer — living on the edge (of the cell)
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Napoletano, F., Baron, O., Vandenabeele, P., Mollereau, B., & Fanto, M. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.12.007 · Cited by 118 · see citing works
The molecular basis of mammary gland development and epithelial differentiation
Slepicka, P. F., Somasundara, A. V. H., & dos Santos, C. O. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.09.014 · Cited by 112 · see citing works
PML: Regulation and multifaceted function beyond tumor suppression
Hsu, K.-S., & Kao, H. (2018) · Cell & Bioscience · doi:10.1186/s13578-018-0204-8 · Cited by 117 · see citing works
Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation
Zwick, R. K., Rudolph, M. C., Shook, B. A., Holtrup, B., Roth, E. M., Lei, V., Keymeulen, A. V., Seewaldt, V. L., Kwei, S. L., Wysolmerski, J. J., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05911-0 · Cited by 110 · see citing works
Autophagy–lysosomal-associated neuronal death in neurodegenerative disease
Nixon, R. A. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02799-7 · Cited by 117 · see citing works
Protease signaling in animal and plant‐regulated cell death
Salvesen, G. S., Hempel, A., & Coll, N. S. (2015) · FEBS Journal · doi:10.1111/febs.13616 · Cited by 104 · see citing works
The role of lysosome in regulated necrosis
Alu, A., Han, X., Ma, X., Wu, M., Wei, Y., & Wei, X. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.07.003 · Cited by 104 · see citing works
Lloyd‐Lewis, B., Davis, F. M., Harris, O. B., Hitchcock, J. R., Lourenço, F. C., Pasche, M., & Watson, C. J. (2016) · Breast Cancer Research · doi:10.1186/s13058-016-0754-9 · Cited by 103 · see citing works
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Jena, M. K., Jaswal, S., Kumar, S., & Mohanty, A. K. (2018) · Developmental Biology · doi:10.1016/j.ydbio.2018.11.002 · Cited by 103 · see citing works
Immunological consequences of kidney cell death
Sarhan, M., von Mäßenhausen, A., Hugo, C., Oberbauer, R. W., & Linkermann, A. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0057-9 · Cited by 98 · see citing works
Tumor-associated macrophage heterogeneity is driven by tissue territories in breast cancer
Laviron, M., Petit, M., Weber-Delacroix, E., Combes, A. J., Arkal, A. R., Barthélémy, S., Courau, T., Hume, D. A., Combadière, C., Krummel, M. F., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110865 · Cited by 95 · see citing works
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Barrueco, R. R., Nekritz, E. A., Bertucci, F., Yu, J., Sanchez-Garcia, F., Zeleke, T. Z., Gorbatenko, A., Birnbaum, D., Ezhkova, E., Cordon‐Cardo, C., et al. (2017) · Genes & Development · doi:10.1101/gad.292318.116 · Cited by 87 · see citing works
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Self-citationWatson, C. J., & Khaled, W. T. (2020) · Development · doi:10.1242/dev.169862 · Cited by 84 · see citing works
Self-citationMartínez‐Fábregas, J., Prescott, A. R., van Kasteren, S. I., Pedrioli, D. M. L., McLean, W. H. I., Moles, A., Reinheckel, T., Poli, V., & Watts, C. K. W. (2018) · Nature Communications · doi:10.1038/s41467-018-07741-6 · Cited by 81 · see citing works
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Hughes, K., & Watson, C. J. (2018) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-018-9395-1 · Cited by 75 · see citing works
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The mTOR–lysosome axis at the centre of ageing
Carosi, J. M., Fourrier, C., Bensalem, J., & Sargeant, T. J. (2021) · FEBS Open Bio · doi:10.1002/2211-5463.13347 · Cited by 66 · see citing works
Self-citationDevelopmental Stage-Specific Distribution of Macrophages in Mouse Mammary Gland
Stewart, T. A., Hughes, K., Hume, D. A., & Davis, F. M. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00250 · Cited by 64 · see citing works
The Lysosome and Intracellular Signalling.
Hesketh, G., Wartosch, L., Davis, L. J., Bright, N. A., & Luzio, J. P. (2018) · Progress in molecular and subcellular biology · doi:10.1007/978-3-319-96704-2_6 · Cited by 36 · see citing works
Hughes, K. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.09.010 · Cited by 48 · see citing works
Akhtar, N., Li, W., Mironov, A., & Streuli, C. H. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.08.005 · Cited by 47 · see citing works
Understanding Susceptibility to Breast Cancer: From Risk Factors to Prevention Strategies
García‐Sancha, N., Corchado‐Cobos, R., & Pérez‐Losada, J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26072993 · Cited by 45 · see citing works
Targeting Cancer Lysosomes with Good Old Cationic Amphiphilic Drugs
Ellegaard, A., Bach, P. B., & Jäättelä, M. (2020) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_2020_56 · Cited by 44 · see citing works
Intracellular metal ion-based chemistry for programmed cell death
You, Y., Guo, Z., Wolter, T., & Hu, Q. (2025) · Chemical Society Reviews · doi:10.1039/d4cs00930d · Cited by 45 · see citing works
Real-Time Monitoring of Lysosomal Membrane Permeabilization Using Acridine Orange
Eriksson, I., Vainikka, L. K., Persson, H. L., & Öllinger, K. M. (2023) · Methods and Protocols · doi:10.3390/mps6040072 · Cited by 43 · see citing works
Otto, P. I., Guimarães, S. E. F., Calus, M. P. L., Vandenplas, J., Machado, M. A., Panetto, J. C. D. C., & da Silva, M. V. G. B. (2020) · Journal of Dairy Science · doi:10.3168/jds.2019-17890 · Cited by 39 · see citing works
Dynamic architectural interplay between leucocytes and mammary epithelial cells
Hitchcock, J. R., Hughes, K., Harris, O. B., & Watson, C. J. (2019) · FEBS Journal · doi:10.1111/febs.15126 · Cited by 38 · see citing works
Self-citationControl of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1
Pihán, P., Lisbona, F., Borgonovo, J. E., Edwards‐Jorquera, S., Nunes, P., Castillo, K., Kepp, O., Urra, H., Saarnio, S., Vihinen, H., et al. (2021) · Science Advances · doi:10.1126/sciadv.abe5469 · Cited by 35 · see citing works
Huang, Y., Huang, X., Yang, Y., Wang, W., Yu, Y., & Qin, Q. (2014) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2014.12.031 · Cited by 37 · see citing works
Zuo, D., Zhou, Z., Wang, H., Zhang, T., Zang, J., Yin, F., Sun, W. Y., Chen, J., Duan, L., Xu, J., et al. (2016) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12957 · Cited by 37 · see citing works
Jaswal, S., Jena, M. K., Anand, V., Jaswal, A., Kancharla, S., Kolli, P., Mandadapu, G., Kumar, S., & Mohanty, A. K. (2022) · Cells · doi:10.3390/cells11203325 · Cited by 36 · see citing works
Mammary Gland Involution Provides a Unique Model to Study the TGF-β Cancer Paradox
Guo, Q., Betts, C. B., Pennock, N. D., Mitchell, E., & Schedin, P. S. (2017) · Journal of Clinical Medicine · doi:10.3390/jcm6010010 · Cited by 35 · see citing works
Calcium signaling in lysosome-dependent cell death
Milani, M., Pihán, P., & Hetz, C. A. (2023) · Cell Calcium · doi:10.1016/j.ceca.2023.102751 · Cited by 34 · see citing works
Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome
Johnson, K. E., Heisel, T. J., Allert, M., Fürst, A., Yerabandi, N., Knights, D., Jacobs, K. M., Lock, E. F., Bode, L., Fields, D. A., et al. (2024) · Cell Genomics · doi:10.1016/j.xgen.2024.100638 · Cited by 37 · see citing works
Lysoptosis is an evolutionarily conserved cell death pathway moderated by intracellular serpins
Luke, C. J., Markovina, S. T., Good, M. L., Wight, I. E., Thomas, B. J., Linneman, J. M., Lanik, W. E., Koroleva, O., Coffman, M. R., Miedel, M. T., et al. (2022) · Communications Biology · doi:10.1038/s42003-021-02953-x · Cited by 34 · see citing works
Studies of postpartum mammary gland involution reveal novel pro-metastatic mechanisms
Wallace, T. R., Tarullo, S. E., Crump, L. S., & Lyons, T. R. (2019) · Journal of Cancer Metastasis and Treatment · doi:10.20517/2394-4722.2019.01 · Cited by 31 · see citing works
The V-ATPase a2 isoform controls mammary gland development through Notch and TGF-β signaling
Pamarthy, S., Mao, L., Katara, G. K., Fleetwood, S., Kulshreshta, A., Gilman‐Sachs, A., & Beaman, K. D. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.347 · Cited by 33 · see citing works
Stewart, T. A., Hughes, K., Stevenson, A. J., Marino, N., Ju, A. L., Morehead, M., & Davis, F. M. (2020) · Journal of Cell Science · doi:10.1242/jcs.248849 · Cited by 33 · see citing works
Stat3-mediated alterations in lysosomal membrane protein composition
Lloyd‐Lewis, B., Krueger, C. C., Sargeant, T. J., D’Angelo, M. E., Deery, M. J., Feret, R., Howard, J. A., Lilley, K. S., & Watson, C. J. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.001777 · Cited by 33 · see citing works
Self-citationLi, L., Sun, B., Gao, Y., Niu, H., Yuan, H., & Lou, H. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.02.026 · Cited by 31 · see citing works
Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism
Lim, C. L., Or, Y. Z., Ong, Z., Chung, H. H., Hayashi, H., Shrestha, S., Chiba, S., Lin, F., & Lin, V. C. L. (2020) · eLife · doi:10.7554/elife.57274 · Cited by 31 · see citing works
Insights Into Ferroptosis, a Novel Target for the Therapy of Cancer
Wang, H., Ju, J., Wang, S., Zhang, Y., Liu, C.-Y., Wang, T., Yu, X. M., Wang, F., Cheng, X.-R., Wang, K., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.812534 · Cited by 29 · see citing works
The Cellular Organization of the Mammary Gland: Insights From Microscopy
Dawson, C. A., & Visvader, J. E. (2021) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-021-09483-6 · Cited by 27 · see citing works
TNFα Post‐Translationally Targets ZnT2 to Accumulate Zinc in Lysosomes
Hennigar, S. R., & Kelleher, S. L. (2015) · Journal of Cellular Physiology · doi:10.1002/jcp.24992 · Cited by 27 · see citing works
Fate decision of satellite cell differentiation and self-renewal by miR-31-IL34 axis
Su, Y., Yu, Y., Liu, C., Zhang, Y., Liu, C., Ge, M., Li, L., Lan, M., Wang, T., Li, M., et al. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0390-x · Cited by 27 · see citing works
ZnT2 is critical for lysosome acidification and biogenesis during mammary gland involution
Rivera, O. C., Hennigar, S. R., & Kelleher, S. L. (2018) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00444.2017 · Cited by 25 · see citing works
Organellar Contacts of Milk Lipid Droplets
Monks, J., Ladinsky, M. S., & McManaman, J. L. (2020) · Contact · doi:10.1177/2515256419897226 · Cited by 25 · see citing works
Romagnoli, M., Bresson, L., Di-Cicco, A., Pérez-Lanzón, M., Legoix, P., Baulande, S., de la Grange, P., Arcangelis, A. D., Georges‐Labouesse, E., Sonnenberg, A., et al. (2020) · Development · doi:10.1242/dev.181552 · Cited by 24 · see citing works
Multidimensional Imaging of Mammary Gland Development: A Window Into Breast Form and Function
Lloyd‐Lewis, B. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00203 · Cited by 22 · see citing works
Self-citationArboccó, F. C. V., Sasso, C. V., Actis, E. A., Carón, R. W., Hapon, M. B., & Jahn, G. A. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.09.023 · Cited by 23 · see citing works
Lee, S., Zhou, Y., Gill, D. L., & Kelleher, S. L. (2018) · Scientific Reports · doi:10.1038/s41598-018-21505-8 · Cited by 23 · see citing works
Nuclear degradation dynamics in a nonapoptotic programmed cell death
Yalonetskaya, A., Mondragon, A. A., Hintze, Z. J., Holmes, S., & McCall, K. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0382-x · Cited by 21 · see citing works
Hitchcock, J. R., Hughes, K., Pensa, S., Lloyd‐Lewis, B., & Watson, C. J. (2022) · Development · doi:10.1242/dev.200162 · Cited by 21 · see citing works
Self-citationDevelopment and Pathology of the Equine Mammary Gland
Hughes, K. (2020) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-020-09471-2 · Cited by 20 · see citing works
Ammah, A. A., Do, D. N., Bissonnette, N., Gévry, N. Y., & Ibeagha-Awemu, E. M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092500 · Cited by 20 · see citing works
Li, Y., Zhang, Y., Gan, Q., Xu, M., Ding, X., Tang, G., Liang, J., Liu, K., Liu, X., Wang, X., et al. (2018) · Protein & Cell · doi:10.1007/s13238-018-0520-0 · Cited by 19 · see citing works
Kobayashi, K., Tsugami, Y., Suzuki, N., Suzuki, T., & Nishimura, T. (2019) · Toxicology in Vitro · doi:10.1016/j.tiv.2019.104741 · Cited by 19 · see citing works
When lipid homeostasis runs havoc: Lipotoxicity links lysosomal dysfunction to autophagy
Tegeder, I., & Kögel, D. (2020) · Matrix Biology · doi:10.1016/j.matbio.2020.11.005 · Cited by 19 · see citing works
Zhang, X., Ding, K., Ji, J., Parajuli, H., Aasen, S. N., Espedal, H., Huang, B., Chen, A., Wang, J., Li, X., et al. (2020) · PubMed Central · Cited by 19 · see citing works
STAT3 Enhances Sensitivity of Glioblastoma to Drug-Induced Autophagy-Dependent Cell Death
Remy, J., Linder, B., Weirauch, U., Day, B. W., Stringer, B. W., Herold‐Mende, C. C., Aigner, A. M., Krohn, K., & Kögel, D. (2022) · Cancers · doi:10.3390/cancers14020339 · Cited by 18 · see citing works
Lysosomal Dysregulation in the Murine App Model of Alzheimer’s Disease
Whyte, L. S., Hassiotis, S., Hattersley, K. J., Hemsley, K. M., Hopwood, J. J., Lau, A. A., & Sargeant, T. J. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2019.12.042 · Cited by 18 · see citing works
Self-citationImmune Cell Contribution to Mammary Gland Development
Vickers, R. R., & Porter, W. W. (2024) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-024-09568-y · Cited by 20 · see citing works
Alveolar cells in the mammary gland: lineage commitment and cell death
Watson, C. J. (2022) · Biochemical Journal · doi:10.1042/bcj20210734 · Cited by 17 · see citing works
Self-citationSurveying the landscape of emerging and understudied cell death mechanisms
Leak, L. B., & Dixon, S. J. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2023.119432 · Cited by 17 · see citing works
Liu, Y., Che, X., Yu, X., Shang, H., Cui, P., Fu, X., Lu, X., Liu, Y., Wu, C., & Yang, J. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04792-x · Cited by 17 · see citing works
Davis, F. M. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.12.007 · Cited by 17 · see citing works
Wang, P., Du, S., Guo, C., Ni, Z., Huang, Z., Deng, N., Bao, H., Deng, W., Lu, J., Kong, S., et al. (2023) · Autophagy · doi:10.1080/15548627.2023.2247747 · Cited by 16 · see citing works
Mammary basal cells: Stars of the show
Gieniec, K. A., & Davis, F. M. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2021.119159 · Cited by 16 · see citing works
The two facets of gp130 signalling in liver tumorigenesis
Schmidt‐Arras, D., Galun, E., & Rose‐John, S. (2021) · Seminars in Immunopathology · doi:10.1007/s00281-021-00861-0 · Cited by 15 · see citing works
Lloyd‐Lewis, B., Gobbo, F., Perkins, M., Jacquemin, G., Huyghe, M., Faraldo, M. M., & Fré, S. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110461 · Cited by 15 · see citing works
Self-citationTranscription Factor Sox4 as a Potential Player in Mammary Gland Involution
Shibayama, H., Yamamoto, T. M., Oshima, K., Matsuda, T., & Nadano, D. (2019) · DNA and Cell Biology · doi:10.1089/dna.2019.4700 · Cited by 14 · see citing works
Geng, Y., Arroyave-Ospina, J. C., Buist‐Homan, M., Plantinga, J. A., Olinga, P., Reijngoud, D., van Vilsteren, F. G. I., Blokzijl, H., Kamps, J. A. A. M., & Moshage, H. J. (2023) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2022.109255 · Cited by 14 · see citing works
Kobayashi, K., Tsugami, Y., Suzuki, N., Suzuki, T., & Nishimura, T. (2020) · Phytomedicine · doi:10.1016/j.phymed.2020.153360 · Cited by 14 · see citing works
From Embryogenesis to Senescence: The Role of Mammary Gland Physiology in Breast Cancer Risk
Lue, J. C., & Radisky, D. C. (2025) · Cancers · doi:10.3390/cancers17050787 · Cited by 16 · see citing works
Jeong, J., Kim, W., Hens, J. R., Dann, P. R., Schedin, P. S., Friedman, P. A., & Wysolmerski, J. J. (2019) · Endocrinology · doi:10.1210/en.2019-00230 · Cited by 13 · see citing works
Got Milk? Identifying and Characterizing Lactation Defects in Genetically-Engineered Mouse Models
Stewart, T. A., & Davis, F. M. (2020) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-020-09467-y · Cited by 13 · see citing works
Mammary mechanobiology: mechanically-activated ion channels in lactation and involutionPreprint
Stewart, T. A., Hughes, K., Stevenson, A. J., Marino, N., Ju, A. L., Morehead, M., & Davis, F. M. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/649038 · Cited by 13 · see citing works
Status of breast cancer detection in young women and potential of liquid biopsy
Stibbards-Lyle, M., Malinovska, J., Badawy, S., Schedin, P. S., & Rinker, K. D. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1398196 · Cited by 12 · see citing works
Majumder, S., Mishra, S., Shinde, N., Cuitiño, M. C., Bauer, M., Ahirwar, D. K., Basree, M. M., Bharti, V., Ormiston, K., Mawalkar, R., et al. (2025) · Breast Cancer Research · doi:10.1186/s13058-024-01933-3 · Cited by 12 · see citing works
Bagdonaitė, R., Žvirblis, R., Dodonova‐Vaitkūnienė, J., & Polita, A. (2025) · JACS Au · doi:10.1021/jacsau.5c00253 · Cited by 12 · see citing works
Hughes, K., Blanck, M., Pensa, S., & Watson, C. J. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.302 · Cited by 12 · see citing works
Self-citation
- Authors
- Sargeant, T. J., Lloyd-Lewis, B., Resemann, H. K., Ramos-Montoya, A., Skepper, J., & Watson, C. J.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Watson, Christine J.
- Venue
- Nature Cell Biology
- Published
- 2014-10-05
- Volume
- 16
- Issue
- 11
- Pages
- 1057-1068
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC4216597
- OpenAlex
- W2022167776
- Cited by
- 168
- References
- 60
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 9 · 2023: 14 · 2022: 21 · 2021: 12 · 2020: 24 · 2019: 14 · 2018: 20 · 2017: 4 · 2016: 13 · 2015: 10 · 2014: 2
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Apollo (University of Cambridge) (acceptedVersion)
- Explore Bristol Research (submittedVersion)
- Funders
- Cancer Research UK
- Medical Research Council (MR/J001023/1)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- STAT3, mammary gland involution, lysosomal membrane permeabilization, milk fat globules, oleic acid, cathepsins, MFG-E8, phagocytosis, triglyceride uptake, mammary epithelial cells, free fatty acids
- MeSH terms
- Animals, Biological Transport, Cathepsins, Epithelial Cells, Female, Glycolipids, Glycoproteins, Lysosomes, Mammary Glands, Animal, Mice, Inbred C57BL, Mice, Transgenic, Phagocytosis, Cell Death, Apoptosis, Mice, Knockout, STAT3 Transcription Factor, Lipid Droplets
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