Investigation of calcineurin B homolgous protein 2 regulation on NHE1. A potential novel therapeutic target to treat non‐small cell lung cancer

The sodium hydrogen exchanger 1 (NHE1) regulates cellular functions including intracellular pH, cell shape, migration and proliferation. NHE1 regulation primarily occurs through protein interactions. Calcineurin B homologous protein 2 (CHP2) activates NHE1 transport and is expressed in carcinoma cells but is poorly expressed in non‐diseased tissues. The goal of this study was to demonstrate the role of NHE1 in invasion of H‐1299 carcinoma cells and to determine if CHP2 regulates NHE1 function. We show that agonist stimulation of H1299 cells increases the invasive potential of the cells by 2.5 fold. However, the inhibition of NHE1 or NHE1 knockdown dramatically decreased the invasion and migration ability of the cells by 80%. Analysis of mRNA expression of paired peripheral, non‐diseased tissue and tumor samples from the same patients revealed a significant 13–243 fold increase of CHP2 expression in five out of seven patients with squamous cell carcinoma. For these patients, NHE1 mRNA expression in diseased tissue was not significantly different from non‐diseased tissue (1.1–3.6 fold change). We also show that CHP2 was expressed in cultured lung cancer cells H460, H69AR, A549 and H358 but not in non‐cancerous lung cells Hs888Lu. These data indicate the NHE1 is essential for invasion and migration in H1299 cells and increased CHP2 gene correlates with lung cancer. In future studies RNA knockdown of CHP2 in H1299 cells will be used to establish CHP2 influence on cellular proliferation, invasion and migration to provide a potential new therapeutic target for NSCLC. Supported by NIH‐1‐R15‐CA 135616‐01.