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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480744/ https://www.ncbi.nlm.nih.gov/pubmed/25797272 |
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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 |
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