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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Autores principales: 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.
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00219525_v217_n8_p2777_Sampayo
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spelling 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
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection 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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