dc.contributor.author |
Barone I |
|
dc.contributor.author |
Vircillo V |
|
dc.contributor.author |
Giordano C |
|
dc.contributor.author |
Gelsomino L |
|
dc.contributor.author |
Győrffy, Balázs |
|
dc.contributor.author |
Tarallo R |
|
dc.contributor.author |
Rinaldi A |
|
dc.contributor.author |
Bruno G |
|
dc.contributor.author |
Caruso A |
|
dc.contributor.author |
Romeo F |
|
dc.contributor.author |
Bonofiglio D |
|
dc.contributor.author |
Andò S |
|
dc.contributor.author |
Catalano S |
|
dc.date.accessioned |
2019-03-20T12:49:53Z |
|
dc.date.available |
2019-03-20T12:49:53Z |
|
dc.date.issued |
2018 |
|
dc.identifier |
85052949912 |
|
dc.identifier.citation |
journalVolume=437;journalTitle=CANCER LETTERS;pagerange=89-99;journalAbbreviatedTitle=CANCER LETT; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/6835 |
|
dc.identifier.uri |
doi:10.1016/j.canlet.2018.08.026 |
|
dc.description.abstract |
Cancer-associated Fibroblasts (CAFs), the principal components of tumor microenvironment, play multiple role in breast cancer progression. We have previously shown an oncosuppressive role of the nuclear Farnesoid X Receptor (FXR) in mammary epithelial cancer cells, here we assessed whether FXR activation may affect CAF tumor-promoting features. We showed that FXR is expressed in human CAFs isolated from four patients and treatment with the selective FXR agonist GW4064 decreased CAF migration, stress-fiber formation and contractility. RNA-sequencing highlighted cell movement and pathways known to govern cell cytoskeleton organization and migration among the most down-regulated functions and ingenuity canonical pathways upon GW4064 treatment. FXR activation reduced expression of different secreted factors. Coculture experiments revealed a reduced growth and motility of breast cancer cells treated with conditioned-media derived from GW4064-treated CAFs. Increased FXR levels in bulk tumors correlated with a longer patient survival. Our results evidence that FXR activation inhibits tumor-stimulatory activities of CAFs by impacting their mechanical properties and their paracrine signaling repertoire, suggesting that nuclear FXR ligands, by targeting both neoplastic cells and supportive stroma, may represent a promising avenue for the future management of breast cancer. © 2018 Elsevier B.V. |
|
dc.format.extent |
89-99 |
|
dc.relation.ispartof |
urn:issn:0304-3835 |
|
dc.title |
Activation of Farnesoid X Receptor impairs the tumor-promoting function of breast cancer-associated fibroblasts |
|
dc.type |
Journal Article |
|
dc.date.updated |
2019-03-06T08:59:46Z |
|
dc.language.rfc3066 |
en |
|
dc.rights.holder |
NULL |
|
dc.identifier.mtmt |
3421387 |
|
dc.identifier.wos |
000447476100009 |
|
dc.identifier.pubmed |
30176263 |
|
dc.contributor.department |
SE/AOK/K/II. Sz. Gyermekgyógyászati Klinika |
|
dc.contributor.department |
MTA TTK/EI/Onkológiai Biomarker Kutatócsoport (Lendület) |
|
dc.contributor.institution |
Semmelweis Egyetem |
|