Cargando…

FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous tumors that need to be molecularly defined to obtain novel therapeutic options. Forkheadbox protein M1 (FOXM1) is a crucial transcription factor in neoplastic cells and has been associated with differentiation and prolifera...

Descripción completa

Detalles Bibliográficos
Autores principales: Briest, Franziska, Berg, Erika, Grass, Irina, Freitag, Helma, Kaemmerer, Daniel, Lewens, Florentine, Christen, Friederike, Arsenic, Ruza, Altendorf-Hofmann, Annelore, Kunze, Almut, Sänger, Jörg, Knösel, Thomas, Siegmund, Britta, Hummel, Michael, Grabowski, Patricia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480744/
https://www.ncbi.nlm.nih.gov/pubmed/25797272
_version_ 1782378186360750080
author Briest, Franziska
Berg, Erika
Grass, Irina
Freitag, Helma
Kaemmerer, Daniel
Lewens, Florentine
Christen, Friederike
Arsenic, Ruza
Altendorf-Hofmann, Annelore
Kunze, Almut
Sänger, Jörg
Knösel, Thomas
Siegmund, Britta
Hummel, Michael
Grabowski, Patricia
author_facet Briest, Franziska
Berg, Erika
Grass, Irina
Freitag, Helma
Kaemmerer, Daniel
Lewens, Florentine
Christen, Friederike
Arsenic, Ruza
Altendorf-Hofmann, Annelore
Kunze, Almut
Sänger, Jörg
Knösel, Thomas
Siegmund, Britta
Hummel, Michael
Grabowski, Patricia
author_sort Briest, Franziska
collection PubMed
description Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous tumors that need to be molecularly defined to obtain novel therapeutic options. Forkheadbox protein M1 (FOXM1) is a crucial transcription factor in neoplastic cells and has been associated with differentiation and proliferation. We found that FOXM1 is strongly associated with tumor differentiation and occurrence of metastases in gastrointestinal NENs. In vitro inhibition by the FOXM1 inhibitor siomycin A led to down-regulation of mitotic proteins and resulted in a strong inhibitory effect. Siomycin A decreased mitosis rate, induced apoptosis in GEP-NEN cell lines and exerts synergistic effects with chemotherapy. FOXM1 is associated with clinical outcome and FOXM1 inhibition impairs survival in vitro. We therefore propose FOXM1 as novel therapeutic target in GEP-NENs.
format Online
Article
Text
id pubmed-4480744
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-44807442015-06-26 FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors Briest, Franziska Berg, Erika Grass, Irina Freitag, Helma Kaemmerer, Daniel Lewens, Florentine Christen, Friederike Arsenic, Ruza Altendorf-Hofmann, Annelore Kunze, Almut Sänger, Jörg Knösel, Thomas Siegmund, Britta Hummel, Michael Grabowski, Patricia Oncotarget Research Paper Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous tumors that need to be molecularly defined to obtain novel therapeutic options. Forkheadbox protein M1 (FOXM1) is a crucial transcription factor in neoplastic cells and has been associated with differentiation and proliferation. We found that FOXM1 is strongly associated with tumor differentiation and occurrence of metastases in gastrointestinal NENs. In vitro inhibition by the FOXM1 inhibitor siomycin A led to down-regulation of mitotic proteins and resulted in a strong inhibitory effect. Siomycin A decreased mitosis rate, induced apoptosis in GEP-NEN cell lines and exerts synergistic effects with chemotherapy. FOXM1 is associated with clinical outcome and FOXM1 inhibition impairs survival in vitro. We therefore propose FOXM1 as novel therapeutic target in GEP-NENs. Impact Journals LLC 2015-03-15 /pmc/articles/PMC4480744/ /pubmed/25797272 Text en Copyright: © 2015 Briest et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Briest, Franziska
Berg, Erika
Grass, Irina
Freitag, Helma
Kaemmerer, Daniel
Lewens, Florentine
Christen, Friederike
Arsenic, Ruza
Altendorf-Hofmann, Annelore
Kunze, Almut
Sänger, Jörg
Knösel, Thomas
Siegmund, Britta
Hummel, Michael
Grabowski, Patricia
FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors
title FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors
title_full FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors
title_fullStr FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors
title_full_unstemmed FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors
title_short FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors
title_sort foxm1: a novel drug target in gastroenteropancreatic neuroendocrine tumors
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480744/
https://www.ncbi.nlm.nih.gov/pubmed/25797272
work_keys_str_mv AT briestfranziska foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT bergerika foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT grassirina foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT freitaghelma foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT kaemmererdaniel foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT lewensflorentine foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT christenfriederike foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT arsenicruza foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT altendorfhofmannannelore foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT kunzealmut foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT sangerjorg foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT knoselthomas foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT siegmundbritta foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT hummelmichael foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors
AT grabowskipatricia foxm1anoveldrugtargetingastroenteropancreaticneuroendocrinetumors