title: FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors.
abstract: 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.
authors: Department of Gastroenterology, Infectious Diseases, Rheumatology CC13, Medizinische Klinik 1, CBF, Germany.|Department of Chemistry and Biochemistry, Freie Universität (FU) Berlin, Germany.
authors: Franziska
authors: F
authors: Briest
authors: Institute of Pathology, CBF, Charité - Universitätsmedizin Berlin, Germany.
authors: Erika
authors: E
authors: Berg
authors: Department of Gastroenterology, Infectious Diseases, Rheumatology CC13, Medizinische Klinik 1, CBF, Germany.|Department of Chemistry and Biochemistry, Freie Universität (FU) Berlin, Germany.
authors: Irina
authors: I
authors: Grass
authors: Department of Gastroenterology, Infectious Diseases, Rheumatology CC13, Medizinische Klinik 1, CBF, Germany.
authors: Helma
authors: H
authors: Freitag
authors: Department of General and Visceral Surgery, Zentralklinik Bad Berka GmbH, Germany.
authors: Daniel
authors: D
authors: Kaemmerer
authors: Department of Gastroenterology, Infectious Diseases, Rheumatology CC13, Medizinische Klinik 1, CBF, Germany.
authors: Florentine
authors: F
authors: Lewens
authors: Department of Gastroenterology, Infectious Diseases, Rheumatology CC13, Medizinische Klinik 1, CBF, Germany.|Institute of Biology, Humboldt-Universität Berlin, Germany.
authors: Friederike
authors: F
authors: Christen
authors: Institute of Pathology, CCM, Charité-Universitätsmedizin Berlin, Germany.
authors: Ruza
authors: R
authors: Arsenic
authors: Department of General, Visceral and Vascular Surgery, Friedrich-Schiller-Universität (FSU) Jena, Germany.
authors: Annelore
authors: A
authors: Altendorf-Hofmann
authors: Institute of Pathology, Bad Berka, Germany.
authors: Almut
authors: A
authors: Kunze
authors: Institute of Pathology, Bad Berka, Germany.
authors: Jörg
authors: J
authors: Sänger
authors: Institute of Pathology, Ludwig-Maximilians-Universität (LMU), Munich, Germany.
authors: Thomas
authors: T
authors: Knösel
authors: Department of Gastroenterology, Infectious Diseases, Rheumatology CC13, Medizinische Klinik 1, CBF, Germany.
authors: Britta
authors: B
authors: Siegmund
authors: Institute of Pathology, CBF, Charité - Universitätsmedizin Berlin, Germany.
authors: Michael
authors: M
authors: Hummel
authors: Department of Gastroenterology, Infectious Diseases, Rheumatology CC13, Medizinische Klinik 1, CBF, Germany.|Department of Internal Oncology and Hematology, Zentralklinik Bad Berka GmbH, Germany.
authors: Patricia
authors: P
authors: Grabowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D055815:Young Adult
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D010455:Peptides; C025311:siomycin
keywords: FOXM1; cancer signaling; differentiation; gastroenteropancreatic neuroendocrine neoplasms; siomycin A