FGF-2 Prevents Cancer Cells from ER Stress-Mediated Apoptosis via Enhancing Proteasome-mediated Nck Degradation

Induction of Endoplasmic Reticulum (ER) stress-mediated apoptosis in cancer cells represents an alternative approach for cancer therapy. Whether fibroblast growth factor 2 (FGF-2)-induced survival signals may interact with ER stress signalling in cancer cells remains elusive. In this work, we showed that pretreatment with FGF-2 decreased the inhibition of DNA synthesis and induction of apoptosis by two different ER stress inducers, tunicamycin (TM) and thapsigargin (TG), 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 CCAAT/-enhancer-binding protein homologous protein (CHOP) expression. We further demonstrated that pretreatment with FGF-2 mediated decrease of TM-induced CHOP expression and apoptosis through extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway. Finally, we demonstrated that FGF-2 promoted proteasome-mediated degradation of Non-catalytic region of tyrosine kinase adaptor protein (Nck), a SH2/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, and decrease of Nck expression prevented TM-induced CHOP expression and apoptosis. In all, our findings provide the first evidence that Nck plays a pivotal role in integrating FGF-2 and ER stress signals to counteract ER stress deleterious impact on cancer cell su...

Source: BJ Cell - March 1, 2013 Category: Biochemistry Authors: B Li, Z Pi, L liu, B Zhang, X Huang, P Hu, E Chevet, P Yi, J Liu Tags: BJ Signal Source Type: research