Blockade of IGF/IGF-1R signaling axis with soluble IGF-1R mutants suppresses the cell proliferation and tumor growth of human osteosarcoma.
Daigui Cao, Lei Yan, Zhenyu Ye, Ling Zhao, Hao Wang, Jing Zhang, Fang He, Linjuan Huang, Deyao Shi, Qing Liu, Na Ni, Mikhail Pakvasa, William Wagstaff, Xia Zhao, Kai Fu, Andrew Tucker, Connie Chen, Russell R. Reid, Rex C. Haydon, Hue H. Luu, Tong‐Chuan He, Zhan Liao
Abstract
, with the greatest inhibition of tumor growth shown by dnIGF1Rα. Mechanistically, the dnIGF1R mutants down-regulated the expression of PI3K/AKT and RAS/RAF/MAPK, BCL2, Cyclin D1 and most EMT regulators, while up-regulating pro-apoptotic genes in human OS cells. Collectively, these findings strongly suggest that the dnIGF1R mutants, especially dnIGF1Rα, may be further developed as novel anticancer agents that target IGF signaling axis with high specificity and efficacy.
Topics & Concepts
Insulin-like growth factor 1 receptorInsulin-like growth factorCancer researchCell growthGrowth factorReceptor tyrosine kinaseOsteosarcomaBiologyTyrosine kinaseReceptorSignal transductionCell biologyBiochemistryCancer, Hypoxia, and MetabolismGrowth Hormone and Insulin-like Growth FactorsCancer-related Molecular Pathways