Abstract 2878: Targeting the CXCL5-CXCR2-CREB signaling axis suppresses growth, survival, and invasion of lung adenocarcinoma.

Abstract

Abstract The role of chemokines and chemokine receptors has been evolving in cancer. Besides their functions in the immune system, they also play a critical role in tumor initiation, promotion and progression. Since the tumor microenvironment play a critical role in cancer development and progression, the immune components of the tumor microenvironment have gained attention in the recent decades for its critical role in tumorigenesis and tumor control. Recent studies have clearly demonstrated the importance of CXCR2 in the development of lung cancer. Our recent studies showed that CXCR2 expression in tumor cells was associated with poor prognosis in non-small cell lung cancer (NSCLC) patients (n=262). Analysis of gene expression profiles from the National Cancer Institute (NCI) Director's Challenge Cohort of in lung adenocarcinoma patients (n=442) revealed that overexpression of CXCR2 ligands and CXCR2 genes was clustered together in approximately 25% of lung adenocarcinoma patients. Expression of CXCR2 and its associated ligand gene cluster in tumor cells was associated with poor prognosis, smoking status, and poor histologic differentiation. Furthermore, CXCL5 was involved as an potent angiogenic factor in NSCLC. The objective of the current study was to establish the role of the CXCL5/CXCR2 axis in tumor growth and invasion and to determine its related molecular mechanisms. In the study, CXCL5 activated the CREB transcription factor via the pERK1/2-p90Rsk-pCREB signaling pathway. In addition, inhibitors of CXCR2 and downstream signal transduction molecules blocked the activation of pERK1/2-pRsk-pCREB signaling molecules. Blockade of the CXCR2 receptor, CXCR2-dependent signal molecules, or CREB resulted in suppression of NSCLC cell growth, survival and invasion. These results suggest that the CXCL5-CXCR2-CREB signaling axis may be a source of potential therapeutic targets in lung adenocarcinoma. . Citation Format: Hee Sun Park, Jong Woo Lee, Pierre Saintigny, Jonathan M. Kurie, Roy S. Herbst, Jaseok Peter Koo. Targeting the CXCL5-CXCR2-CREB signaling axis suppresses growth, survival, and invasion of lung adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2878. doi:10.1158/1538-7445.AM2013-2878