Cell surface protein C23 affects EGF-EGFR induced activation of ERK and PI3K-AKT pathways.

The epidermal growth factor (EGF) pathway has been reported as canonical causes in cancer development. Meanwhile, the involvement of C23 in multiple signaling pathways has been also investigated (Lv et al., 2014). However, the effect of C23 on EGF pathway in glioblastoma is not fully characterized. In the present study, C23 and the epidermal growth factor receptor (EGFR) of U251 cell line were inhibited by C23 and EGFR antibodies, respectively; and then C23 and EGFR siRNAs were used to knock down endogenous C23 and EGFR, respectively. In addition, soft-agar and MTT assay were also introduced. Compared with control, either C23 or EGFR antibodies efficiently repressed the phosphorylation levels of ERK1/2 (p<0.000) and AKT (p<0.000). Similarly, either C23 or EGFR siRNAs indeed resulted in C23 and EGFR knockdown, and further suppressed the expression of p-ERK1/2 and p-AKT. Most importantly, immunoprecipitation revealed C23 interacted with EGFR once U251 was exposed to EGF treatment. In addition, the MTT and soft-agar assay also identified that C23 or EGFR siRNAs could obviously affected cell growth (p=0.004) and invasiveness, as cell viability and colony formation decreased markedly. Our results suggest that C23 plays a crucial role in activation of EGF-induced ERK and PI3K-AKT pathways via interacting with EGFR; furthermore, C23 could be indicative of an important factor in glioblastoma development and a useful target for glioblastoma treatment.