Assessment of insulin-like growth factor 1 receptor as an oncogene in esophageal squamous cell carcinoma and its potential implication in chemotherapy

Abstract

Insulin-like growth factor-1 receptor (IGF-1R) is a tyrosine kinase receptor implicated in the pathogenesis of multiple cancers. After ligand binding, IGF-1R can initiate the activation of the PI3K/AKT/mTOR and Ras/Raf/MEK/ MAPK pathways to modulate cell proliferation, survival, differentiation, motility, invasion and angiogenesis. IGF-1R is a prerequisite for tumor progression and is one of the most attractive targets for therapeutic interventions in several types of cancer. In the present study, we determined the expression of IGF-1R in an esophageal squamous cell carcinoma (ESCC) cohort, investigated the detailed function of IGF-1R and screened the potential application of IGF-1R in the clinic. We verified the higher expression of IGF-1R in ESCC tumor tissues as compared to adjacent normal tissues. We also found that high expression of IGF-1R was associated with advanced tumor progression. We used ESCC cell lines and a mouse xenograft model to detect the function of IGF-1R in vitro and in vivo. Our results suggest the oncogenic function of IGF-1R in regulating cell proliferation, clonogenesis, the cell cycle and apoptosis. In addition, we found that IGF-1R was associated with the response to standard chemotherapy drugs 5-FU and cisplatin in an ESCC cell line. More importantly, we confirmed that the serum concentration of IGF-1/IGFBP3 can be used for predicting response to chemotherapy, and increased serum levels of IGF-1 and IGFBP-3 are associated with significantly higher rates of tumor response. In the present study, we demonstrated that IGF-1R is an important oncogene in ESCC and can be used to detect the chemotherapeutic response.