Cargando…
FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells
Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa). Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors) promote BCa cell growth with the strongest eff...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964976/ https://www.ncbi.nlm.nih.gov/pubmed/28869838 http://dx.doi.org/10.1016/j.neo.2017.07.006 |
_version_ | 1783325276194734080 |
---|---|
author | Turczyk, Lukasz Kitowska, Kamila Mieszkowska, Magdalena Mieczkowski, Kamil Czaplinska, Dominika Piasecka, Dominika Kordek, Radzisław Skladanowski, Andrzej C. Potemski, Piotr Romanska, Hanna M. Sadej, Rafal |
author_facet | Turczyk, Lukasz Kitowska, Kamila Mieszkowska, Magdalena Mieczkowski, Kamil Czaplinska, Dominika Piasecka, Dominika Kordek, Radzisław Skladanowski, Andrzej C. Potemski, Piotr Romanska, Hanna M. Sadej, Rafal |
author_sort | Turczyk, Lukasz |
collection | PubMed |
description | Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa). Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors) promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization. We also identified activation of PI3K/AKT signaling targeting ER-Ser167 and regulation of Bcl-2 expression as a mediator of FGFR2-promoted resistance to tamoxifen. Analysis of tissue samples from patients with invasive ductal carcinoma revealed an inversed correlation between expression of FGFR2 and ER, thus supporting our in vitro data. These results unveil the complexity of ER regulation by FGFR2-mediated signaling likely to be associated with BCa resistance to endocrine therapy. |
format | Online Article Text |
id | pubmed-5964976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-59649762018-05-31 FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells Turczyk, Lukasz Kitowska, Kamila Mieszkowska, Magdalena Mieczkowski, Kamil Czaplinska, Dominika Piasecka, Dominika Kordek, Radzisław Skladanowski, Andrzej C. Potemski, Piotr Romanska, Hanna M. Sadej, Rafal Neoplasia Original article Signaling mediated by growth factors receptors has long been suggested as one of the key factors responsible for failure of endocrine treatment in breast cancer (BCa). Herein we present that in the presence of tamoxifen, FGFs (Fibroblast Growth Factors) promote BCa cell growth with the strongest effect being produced by FGF7. FGFR2 was identified as a mediator of FGF7 action and the FGFR2-induced signaling was found to underlie cancer-associated fibroblasts-dependent resistance to tamoxifen. FGF7/FGFR2-triggered pathway was shown to induce ER phosphorylation, ubiquitination and subsequent ER proteasomal degradation which counteracted tamoxifen-promoted ER stabilization. We also identified activation of PI3K/AKT signaling targeting ER-Ser167 and regulation of Bcl-2 expression as a mediator of FGFR2-promoted resistance to tamoxifen. Analysis of tissue samples from patients with invasive ductal carcinoma revealed an inversed correlation between expression of FGFR2 and ER, thus supporting our in vitro data. These results unveil the complexity of ER regulation by FGFR2-mediated signaling likely to be associated with BCa resistance to endocrine therapy. Neoplasia Press 2017-09-01 /pmc/articles/PMC5964976/ /pubmed/28869838 http://dx.doi.org/10.1016/j.neo.2017.07.006 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Turczyk, Lukasz Kitowska, Kamila Mieszkowska, Magdalena Mieczkowski, Kamil Czaplinska, Dominika Piasecka, Dominika Kordek, Radzisław Skladanowski, Andrzej C. Potemski, Piotr Romanska, Hanna M. Sadej, Rafal FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells |
title | FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells |
title_full | FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells |
title_fullStr | FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells |
title_full_unstemmed | FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells |
title_short | FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells |
title_sort | fgfr2-driven signaling counteracts tamoxifen effect on erα-positive breast cancer cells |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964976/ https://www.ncbi.nlm.nih.gov/pubmed/28869838 http://dx.doi.org/10.1016/j.neo.2017.07.006 |
work_keys_str_mv | AT turczyklukasz fgfr2drivensignalingcounteractstamoxifeneffectonerapositivebreastcancercells AT kitowskakamila fgfr2drivensignalingcounteractstamoxifeneffectonerapositivebreastcancercells AT mieszkowskamagdalena fgfr2drivensignalingcounteractstamoxifeneffectonerapositivebreastcancercells AT mieczkowskikamil fgfr2drivensignalingcounteractstamoxifeneffectonerapositivebreastcancercells AT czaplinskadominika fgfr2drivensignalingcounteractstamoxifeneffectonerapositivebreastcancercells AT piaseckadominika fgfr2drivensignalingcounteractstamoxifeneffectonerapositivebreastcancercells AT kordekradzisław fgfr2drivensignalingcounteractstamoxifeneffectonerapositivebreastcancercells AT skladanowskiandrzejc fgfr2drivensignalingcounteractstamoxifeneffectonerapositivebreastcancercells AT potemskipiotr fgfr2drivensignalingcounteractstamoxifeneffectonerapositivebreastcancercells AT romanskahannam fgfr2drivensignalingcounteractstamoxifeneffectonerapositivebreastcancercells AT sadejrafal fgfr2drivensignalingcounteractstamoxifeneffectonerapositivebreastcancercells |