CD73 Is Regulated by the EGFR-ERK Signaling Pathway in Non-small Cell Lung Cancer.

Abstract

Successful therapy of EGFR-mutant NSCLC remains a challenging task despite initial benefits with the usage of EGFR tyrosine kinase inhibitors. Cancer immunotherapy has shown promising results in certain tumors, but response rate in EGFR-mutant NCLC is low, because these tumors are thought to have weak immunogenicity. We used data from in vivo NSCLC databases as well as from in vitro cell culture experiments to investigate the regulation of CD73 by EGFR. EGFR expression was correlated with CD73 expression in patients' datasets, with EGFR-mutant tumors showing higher expression than their EGFR wildtype counterparts. Treatment of EGFR-mutant NSCLC cell lines with EGFR TKI reduced expression of CD73 at both mRNA and protein level. Among EGFR downstream signaling pathways, the Ras-Raf-ERK pathway was involved in the regulation of CD73 expression directly via ERK1/2 without the engagement of RSKs or MSKs. The results of this study may provide novel therapeutic strategies for the treatment of oncogene-driven NSCLC.