Glycoprotein nonmetastatic melanoma protein B (GPNMB) promotes the progression of brain glioblastoma via Na+/K+-ATPase.
Glycoprotein nonmetastatic melanoma protein B (GPNMB), which is involved in invasion and metastasis, was found to be overexpressed in various cancers. High levels of GPNMB and Na+/K+-ATPase α subunits are associated with a poor prognosis in glioblastoma patients. We showed that GPNMB interacts with Na+/K+-ATPase α subunits to activate PI3K/Akt and MEK/ERK pathways. However, it remains unclear whether the interaction of GPNMB and Na+/K+-ATPase α subunits is involves in progression of glioma. The tumor size induced by the injection of glioma GL261 cells was larger in transgenic mice overexpressing GPNMB when compared with wild-type mice. Additionally, the interaction of GPNMB and Na+/K+-ATPase α subunits was identified in the murine glioma model and in the tumors of glioblastoma patients. Ouabain, a Na+/K+-ATPase inhibitor, suppressed the glioma growth induced by the injection of glioma cells in the transgenic mice overexpressing GPNMB and blocked the GPNMB-induced migration of glioma cells. These findings indicate that GPNMB promotes glioma growth via Na+/K+-ATPase α subunits. Thus, the interaction between GPNMB and Na+, K+-ATPase α subunits represents a novel therapeutic target for the treatment of brain glioblastomas.
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, 501-1196, Japan.
Yoko
Y
Ono
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, 501-1196, Japan.
Shinsuke
S
Chiba
Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan.
Hirohito
H
Yano
Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan.
Noriyuki
N
Nakayama
Department of Pathology Diagnosis, Matsunami General Hospital, Gifu, 501-6062, Japan.
Masanao
M
Saio
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, 501-1196, Japan.
Kazuhiro
K
Tsuruma
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, 501-1196, Japan.
Masamitsu
M
Shimazawa
Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, 501-1194, Japan.
Toru
T
Iwama
Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, 501-1196, Japan. Electronic address: hidehara@gifu-pu.ac.jp.
Hideaki
H
Hara
D000368:Aged; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D005136:Eye Proteins; C503042:GPNMB protein, human; C445671:Gpnmb protein, mouse; D008562:Membrane Glycoproteins; D000254:Sodium-Potassium-Exchanging ATPase
GL261 cells; Glioblastoma; Glioma; Glycoprotein nonmetastatic melanoma B (GPNMB); Na+, K+-ATPase α subunits