The nuclear localization signal is required for nuclear GPER translocation and function in breast Cancer-Associated Fibroblasts (CAFs)

•GPER localizes into the nucleus of CAFs.•A NLS motif within the GPER sequence is necessary for the nuclear shuttle of GPER.•Nuclear GPER binds to ATRS sequences located on the c-fos and CTGF promoter regions.•Nuclear GPER mediates c-fos and CTGF expression and cell migration induced by E2. Cancer a...

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Veröffentlicht in:	Molecular and cellular endocrinology Jg. 376; H. 1-2; S. 23 - 32
Hauptverfasser:	Pupo, Marco, Vivacqua, Adele, Perrotta, Ida, Pisano, Assunta, Aquila, Saveria, Abonante, Sergio, Gasperi-Campani, Anna, Pezzi, Vincenzo, Maggiolini, Marcello
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Ireland Elsevier Ireland Ltd 25.08.2013
Schlagworte:	Active Transport, Cell Nucleus - drug effects Active Transport, Cell Nucleus - genetics Breast Breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Cancer Cancer-associated fibroblasts Cell Movement Cell Nucleus - drug effects Cell Nucleus - metabolism Cell Nucleus - ultrastructure Cell Proliferation Connective Tissue Growth Factor - genetics Connective Tissue Growth Factor - metabolism estrogen receptors Estrogen signaling Estrogens Estrogens - pharmacology Female Fibroblasts Fibroblasts - drug effects Fibroblasts - metabolism Fibroblasts - pathology gene expression regulation Gene Expression Regulation, Neoplastic genes GPER Humans Karyopherins - genetics Karyopherins - metabolism Localization neoplasm cells Nuclear localization signal nuclear localization signals Nuclear Localization Signals - chemistry Nuclear Localization Signals - metabolism Nuclei physiological transport Position (location) Primary Cell Culture Proto-Oncogene Proteins c-fos - genetics Proto-Oncogene Proteins c-fos - metabolism Receptors, Estrogen - genetics Receptors, Estrogen - metabolism Receptors, G-Protein-Coupled - genetics Receptors, G-Protein-Coupled - metabolism Signal Transduction Tumor Microenvironment - genetics Tumors Nuclear localization signal Cancer-associated fibroblasts Breast cancer Estrogen signaling GPER
ISSN:	0303-7207, 1872-8057, 1872-8057
Online-Zugang:	Volltext
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Zusammenfassung:	•GPER localizes into the nucleus of CAFs.•A NLS motif within the GPER sequence is necessary for the nuclear shuttle of GPER.•Nuclear GPER binds to ATRS sequences located on the c-fos and CTGF promoter regions.•Nuclear GPER mediates c-fos and CTGF expression and cell migration induced by E2. Cancer associated fibroblasts (CAFs) actively contribute to the growth and invasion of cancer cells. In recent years, the G protein estrogen receptor (GPER) has been largely involved in the estrogenic signals in diverse types of normal and tumor cells. In CAFs, GPER was localized into the nucleus, however the molecular mechanisms which regulate its nuclear shuttle remain to be clarified. In the present study, we demonstrate that in breast CAFs GPER translocates into the nucleus through an importin-dependent mechanism. Moreover, we show that a nuclear localization signal is involved in the nuclear import of GPER, in the up-regulation of its target genes c-fos and CTGF and in the migration of CAFs induced by estrogens. Our data provide novel insights into the nuclear localization and function of GPER in CAFs toward a better understanding of the estrogen action elicited through these key players of the tumor microenvironment.
Bibliographie:	http://dx.doi.org/10.1016/j.mce.2013.05.023 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0303-7207 1872-8057 1872-8057
DOI:	10.1016/j.mce.2013.05.023