Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells

Autor: Fernando D. Stefani, Rocío Guadalupe Sampayo, Kate Thi, Alfredo Cáceres, William C. Hines, Luciano A. Masullo, Ianina L. Violi, Dante R. Chialvo, Matthew G. Rubashkin, Mina J. Bissell, Valerie M. Weaver, Jonathon N. Lakins, Andrés Martin Toscani, Marina Simian, Federico Coluccio Leskow
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
receptor
Estrogen receptor
Medical and Health Sciences
Models
Tumor Microenvironment
estrogen
Research Articles
Cancer
Tumor
Integrin beta1
Patología
purl.org/becyt/ford/3.1 [https]
Biological Sciences
3. Good health
Cell biology
Extracellular Matrix
Protein Transport
Medicina Básica
MCF-7 Cells
purl.org/becyt/ford/3 [https]
CIENCIAS MÉDICAS Y DE LA SALUD
medicine.drug_class
Endosome
1.1 Normal biological development and functioning
Integrin
Endosomes
Biology
Endocytosis
Models
Biological
Article
Cell Line
03 medical and health sciences
breast cancer
Underpinning research
fibronectin
Cell Line
Tumor
medicine
Humans
Tumor microenvironment
Estrogen Receptor alpha
Cell Biology
Biological
Fibronectins
Fibronectin
030104 developmental biology
Tumor progression
Estrogen
Proteolysis
biology.protein
Lysosomes
Developmental Biology
Zdroj: CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
The Journal of cell biology, vol 217, iss 8
The Journal of Cell Biology
Sampayo, RG; Toscani, AM; Rubashkin, MG; Thi, K; Masullo, LA; Violi, IL; et al.(2018). Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells. Journal of Cell Biology, 217(8), 2777-2798. doi: 10.1083/jcb.201703037. UCSF: Retrieved from: http://www.escholarship.org/uc/item/3zs6n2gd
Popis: Among ERα-positive breast cancers, approximately half fail to respond to endocrine therapy, and the causes of this resistance are unknown. Sampayo et al. show that fibronectin (FN) influences the trafficking of ERα-positive vesicles. FN promotes ERα localization in Rab11+ vesicles, rescues ERα from lysosomal degradation, and reinforces ERα trafficking to the nucleus and transcriptional activity in tumor 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 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.
Databáze: OpenAIRE
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