Evaluating the Role of the Na+‐H+ Exchanger Isoform 1 (NHE1) in Non‐small Cell Lung Cancer

Abstract

Lung cancer is a debilitating disease with 222,000 new cases diagnosed each year and causing 156,000 deaths each year in the United States. Approximately 80% of lung cancers are categorized as non‐small cell lung cancer (NSCLC). Of these NSCLCs, 50% are comprised of adenocarcinomas, or tumors that originated within glandular epithelium, while 30% are due to squamous cell carcinomas, or a cancer that began at in a squamous epithelial lining. The Na+‐H+ Exchanger Isoform 1 (NHE1) acts as a key regulator in cellular proliferation, migration, and metastasis in a variety of solid tumors. NHE1 exchanges 1 extracellular Na+ ion for 1 intracellular H+ ion driving changes in both intracellular and extracellular pH in these developing tumors. To evaluate the role of NHE1 in NSCLC, we employed three cells types: 1) NCI‐H1299 a carcinoma cell line, 2) NCI‐H520 a squamous cell carcinoma cell line, and 3) NCI‐H23 and adenocarcinoma cell line. For each cell type, changing the media conditions from 0.5% serum to 10% serum increased the rate of cell proliferation 2 to 3 fold. This increased proliferation was blocked when the NHE1 inhibitors EIPA (ethylisopropylamiloride) or cariporide were present. Similarly, the change in serum concentration increase cell migrations rates in an NHE1‐dependent manner. To further evaluate the role of NHE1 in these cells, western blot analysis was completed to evaluate NHE1 expression in both low and normal serum conditions for each cell type. We also employed CRISPR‐Cas9 technology to develop an NHE1‐knockout (NHE1‐KO) cell line for each cell type. The rates of cell proliferation and migration where then evaluated in the NHE1‐KO cells as compared to NHE1 expressing cells.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.