Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells
Estrogen receptor α (ERα) is expressed in tissues as diverse as brains and mammary glands. In breast cancer, ERα is a key regulator of tumor progression. Therefore, understanding what activates ERα is critical for cancer treatment in particular and cell biology in general. Using biochemical approach...
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todo:paper_00219525_v217_n8_p2777_Sampayo2023-10-03T14:23:29Z Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells Sampayo, R.G. Toscani, A.M. Rubashkin, M.G. Thi, K. Masullo, L.A. Violi, I.L. Lakins, J.N. Cáceres, A. Hines, W.C. Leskow, F.C. Stefani, F.D. Chialvo, D.R. Bissell, M.J. Weaver, V.M. Simian, M. beta1 integrin estrogen estrogen receptor alpha fibronectin Article biochemical analysis breast cancer breast tissue cancer cell cell compartmentalization cell fate cell vacuole controlled study endocytosis endosome estrogen activity extracellular matrix human human cell human tissue intracellular transport lysosome microscopy priority journal protein degradation protein function protein localization protein protein interaction signal transduction Estrogen receptor α (ERα) is expressed in tissues as diverse as brains and mammary glands. In breast cancer, ERα is a key regulator of tumor progression. Therefore, understanding what activates ERα is critical for cancer treatment in particular and cell biology in general. Using biochemical approaches and superresolution microscopy, we show that estrogen drives membrane ERα into endosomes in breast cancer cells and that its fate is determined by the presence of fibronectin (FN) in the extracellular matrix; it is trafficked to lysosomes in the absence of FN and avoids the lysosomal compartment in its presence. In this context, FN prolongs ERα half-life and strengthens its transcriptional activity. We show that ERα is associated with β1-integrin at the membrane, and this integrin follows the same endocytosis and subcellular trafficking pathway triggered by estrogen. Moreover, ERα+ vesicles are present within human breast tissues, and colocalization with β1-integrin is detected primarily in tumors. Our work unravels a key, clinically relevant mechanism of microenvironmental regulation of ERα signaling. © 2018 Sampayo et al. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00219525_v217_n8_p2777_Sampayo |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
beta1 integrin estrogen estrogen receptor alpha fibronectin Article biochemical analysis breast cancer breast tissue cancer cell cell compartmentalization cell fate cell vacuole controlled study endocytosis endosome estrogen activity extracellular matrix human human cell human tissue intracellular transport lysosome microscopy priority journal protein degradation protein function protein localization protein protein interaction signal transduction |
| spellingShingle |
beta1 integrin estrogen estrogen receptor alpha fibronectin Article biochemical analysis breast cancer breast tissue cancer cell cell compartmentalization cell fate cell vacuole controlled study endocytosis endosome estrogen activity extracellular matrix human human cell human tissue intracellular transport lysosome microscopy priority journal protein degradation protein function protein localization protein protein interaction signal transduction Sampayo, R.G. Toscani, A.M. Rubashkin, M.G. Thi, K. Masullo, L.A. Violi, I.L. Lakins, J.N. Cáceres, A. Hines, W.C. Leskow, F.C. Stefani, F.D. Chialvo, D.R. Bissell, M.J. Weaver, V.M. Simian, M. Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells |
| topic_facet |
beta1 integrin estrogen estrogen receptor alpha fibronectin Article biochemical analysis breast cancer breast tissue cancer cell cell compartmentalization cell fate cell vacuole controlled study endocytosis endosome estrogen activity extracellular matrix human human cell human tissue intracellular transport lysosome microscopy priority journal protein degradation protein function protein localization protein protein interaction signal transduction |
| description |
Estrogen receptor α (ERα) is expressed in tissues as diverse as brains and mammary glands. In breast cancer, ERα is a key regulator of tumor progression. Therefore, understanding what activates ERα is critical for cancer treatment in particular and cell biology in general. Using biochemical approaches and superresolution microscopy, we show that estrogen drives membrane ERα into endosomes in breast cancer cells and that its fate is determined by the presence of fibronectin (FN) in the extracellular matrix; it is trafficked to lysosomes in the absence of FN and avoids the lysosomal compartment in its presence. In this context, FN prolongs ERα half-life and strengthens its transcriptional activity. We show that ERα is associated with β1-integrin at the membrane, and this integrin follows the same endocytosis and subcellular trafficking pathway triggered by estrogen. Moreover, ERα+ vesicles are present within human breast tissues, and colocalization with β1-integrin is detected primarily in tumors. Our work unravels a key, clinically relevant mechanism of microenvironmental regulation of ERα signaling. © 2018 Sampayo et al. |
| format |
JOUR |
| author |
Sampayo, R.G. Toscani, A.M. Rubashkin, M.G. Thi, K. Masullo, L.A. Violi, I.L. Lakins, J.N. Cáceres, A. Hines, W.C. Leskow, F.C. Stefani, F.D. Chialvo, D.R. Bissell, M.J. Weaver, V.M. Simian, M. |
| author_facet |
Sampayo, R.G. Toscani, A.M. Rubashkin, M.G. Thi, K. Masullo, L.A. Violi, I.L. Lakins, J.N. Cáceres, A. Hines, W.C. Leskow, F.C. Stefani, F.D. Chialvo, D.R. Bissell, M.J. Weaver, V.M. Simian, M. |
| author_sort |
Sampayo, R.G. |
| title |
Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells |
| title_short |
Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells |
| title_full |
Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells |
| title_fullStr |
Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells |
| title_full_unstemmed |
Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells |
| title_sort |
fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells |
| url |
http://hdl.handle.net/20.500.12110/paper_00219525_v217_n8_p2777_Sampayo |
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