PuSH - Publikationsserver des Helmholtz Zentrums München

Leinhäuser, I. ; Richter, A. ; Lee, M.S. ; Höfig, I. ; Anastasov, N. ; Fend, F.* ; Ercolino, T.* ; Mannelli, M.* ; Gimenez-Roqueplo, A.P.* ; Robledo, M.* ; de Krijger, R.R.* ; Beuschlein, F.* ; Atkinson, M.J. ; Pellegata, N.S.

Oncogenic features of the Bone Morphogenic Protein 7 (BMP7) in pheochromocytoma.

Oncotarget 6, 39111-39126 (2015)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BMP7 is a growth factor playing pro- or anti-oncogenic roles in cancer in a cell type-dependent manner. We previously reported that the BMP7 gene is overexpressed in pheochromocytomas (PCCs) developing in MENX-affected rats and human patients. Here, analyzing a large cohort of PCC patients, we found that 72% of cases showed elevated levels of the BMP7 protein. To elucidate the role of BMP7 in PCC, we modulated its levels in PCC cell lines (overexpression in PC12, knockdown in MPC and MTT cells) and conducted functional assays. Active BMP signaling promoted cell proliferation, migration, and invasion, and sustained survival of MENX rat primary PCC cells. In PCC, BMP7 signals through the PI3K/AKT/mTOR pathway and causes integrin β1 up-regulation. Silencing integrin β1 in PC12 cells suppressed BMP7-mediated oncogenic features. Treatment of MTT cells with DMH1, a novel BMP antagonist, suppressed proliferation and migration. To verify the clinical applicability of our findings, we evaluated a dual PI3K/mTOR inhibitor (NVP-BEZ235) in MENX-affected rats in vivo. PCCs treated with NVP-BEZ235 had decreased proliferation and integrin β1 levels, and higher apoptosis. Altogether, BMP7 activates pro-oncogenic pathways in PCC. Downstream effectors of BMP7-mediated signaling may represent novel targets for treating progressive/inoperable PCC, still orphan of effective therapy.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
6.359
1.250
10
8
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Menx Rats ; Pi3k Pathway ; Bone Morphogenic Protein 7 ; Integrin Beta 1 ; Pheochromocytoma
Sprache englisch
Veröffentlichungsjahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 1949-2553
e-ISSN 1949-2553
Zeitschrift OncoTarget
Quellenangaben Band: 6, Heft: 36, Seiten: 39111-39126 Artikelnummer: , Supplement: ,
Verlag Impact Journals LLC
Begutachtungsstatus Peer reviewed
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30202 - Environmental Health
Forschungsfeld(er) Enabling and Novel Technologies
Radiation Sciences
PSP-Element(e) G-500300-001
G-500200-001
PubMed ID 26337467
Scopus ID 84948845037
Erfassungsdatum 2015-09-06