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

BACKGROUND/AIM: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. MATERIALS AND METHODS: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. RESULTS: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. CONCLUSION:The results of this study may provide novel therapeutic strategies for the treatment of oncogene-driven NSCLC.

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