title: FGF-2 prevents cancer cells from ER stress-mediated apoptosis via enhancing proteasome-mediated Nck degradation.
abstract: Induction of ER (endoplasmic reticulum) stress-mediated apoptosis in cancer cells represents an alternative approach for cancer therapy. Whether FGF-2 (fibroblast growth factor 2)-induced survival signals may interact with ER stress signalling in cancer cells remains elusive. In the present study, we showed that pretreatment with FGF-2 decreased the inhibition of DNA synthesis and induction of apoptosis by two different ER stress inducers, TM (tunicamycin) and TG (thapsigargin), in both human hepatoblastoma HepG2 cells and breast cancer MCF-7 cells. Pretreatment with FGF-2 prevented ER stress-mediated apoptosis by decreasing ER stress-induced CHOP [C/EBP (CCAAT/enhancer-binding protein)-homologous protein] expression. We further demonstrated that pretreatment with FGF-2 mediated the decrease in TM-induced CHOP expression and apoptosis through ERK1/2 (extracellular-signal-regulated kinases 1 and 2) pathway. Finally, we demonstrated that FGF-2 promoted proteasome-mediated degradation of Nck (non-catalytic region of tyrosine kinase adaptor protein), an SH (Src homology) 2/SH3-containing adaptor protein. Whereas overexpression of Nck1 decreased FGF-2-induced ERK1/2 phosphorylation to inhibit the effect of FGF-2 on TM-induced CHOP expression and apoptosis, a decrease in Nck expression prevented TM-induced CHOP expression and apoptosis. Taken together, the findings of the present study provide the first evidence that Nck plays a pivotal role in integrating FGF-2 and ER stress signals to counteract the ER stress deleterious effect on cancer cell survival.
authors: Sino-France Laboratory of Cellular Signalling, Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, 430074 Wuhan, Hubei, China.
authors: Bin
authors: B
authors: Li
authors: Zhenjun
authors: Z
authors: Pi
authors: Lei
authors: L
authors: Liu
authors: Bi
authors: B
authors: Zhang
authors: Xiang
authors: X
authors: Huang
authors: Ping
authors: P
authors: Hu
authors: Eric
authors: E
authors: Chevet
authors: Ping
authors: P
authors: Yi
authors: Jianfeng
authors: J
authors: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D009363:Neoplasm Proteins / Q000502:physiology*; D015513:Oncogene Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C078332:Nck protein; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D016222:Fibroblast Growth Factor 2; D046988:Proteasome Endopeptidase Complex