Research Papers:

Nuclear translocation of fibroblast growth factor-2 (FGF2) is regulated by Karyopherin-β2 and Ran GTPase in human glioblastoma cells

Feng Wang _, Lijun Yang, Lin Shi, Qian Li, Gengshen Zhang, Jianliang Wu, Jun Zheng and Baohua Jiao

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Oncotarget. 2015; 6:21468-21478. https://doi.org/10.18632/oncotarget.4097

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Feng Wang1, Lijun Yang1, Lin Shi2, Qian Li3, Gengshen Zhang1, Jianliang Wu1, Jun Zheng1, Baohua Jiao1

1Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China

2Department of Neurosurgery, The Second Hospital of Baoding City, Baoding 071051, China

3Department of Physiology, Hebei Medical University, Shijiazhuang 050000, China

Correspondence to:

Feng Wang, e-mail: fwang1111@163.com

Keywords: fibroblast growth factor (FGF), glioblastoma, nuclear translocation, phosphatase and tensin homolog (PTEN), small GTPase

Received: March 23, 2015     Accepted: May 13, 2015     Published: May 27, 2015


Human glioblastoma multiforme (GBM) is the most malignant tumor of the central nervous system (CNS). Fibroblast growth factor-2 (FGF2) belongs to the FGF superfamily and functions as a potential oncoprotein in GBM. FGF2 has low molecular weight (18K) and high molecular weight (HMW) isoforms. Nuclear accumulation of HMW-FGF2 strongly promotes glioblastoma cell proliferation, yet mechanism governing such cellular distribution remains unexplored. We investigated the mechanisms regulating FGF2 cellular localization in T98G human brain glioblastoma cells. We found HMW-FGF2, but not 18K-FGF2, is primarily located in the nucleus and interacts with nuclear transport protein Karyopherin-β2/Transportin (Kapβ2). SiRNA-directed Kapβ2 knockdown significantly reduced HMW-FGF2′s nuclear translocation. Moreover, inhibiting Ran GTPase activity also resulted in decreased HMW-FGF2 nuclear accumulation. Proliferation of T98G cells is greatly enhanced with transfections HMW-FGF2. Decreased PTEN expression and activated Akt signaling were observed upon HMW-FGF2 overexpression and might mediate pro-survival effect of FGF2. Interestingly, addition of nuclear localization signal (NLS) to 18K-FGF2 forced its nuclear import and dramatically increased cell proliferation and Akt activation. These findings demonstrated for the first time the molecular mechanisms for FGF2′s nuclear import, which promotes GBM cell proliferation and survival, providing novel insights to the development of GBM treatments.

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