Polyisoprenylated methylated protein methyl esterase as a potential novel target in lung cancer therapy

Abstract

Polyisoprenylated monomeric G‐proteins such as Ras, Rho and Rac play important roles in lung carcinogenesis. Targeting the polyisoprenylation pathway enzymes presents therapeutic opportunities but polyisoprenylated methylated protein methyl esterase (PMPMEase) has not been explored. PMPMEase expression and activity were investigated in lung cancer cells, tissues and tissue microarrays (TMAs). PMPMEase activity was significantly elevated in lung cancer cases relative to normal adjacent tissues (p < 0.001), correlating with PMPMEase protein levels. Intense PMPMEase immunoreactivity was observed in 88.3% of over 400 lung cancer cases on TMAs (p < 0.0001). Specific PMPMEase activities in A549 and H460 cells were 1.6‐ and 1.5‐fold higher than in WI‐38 cells, respectively. Exposure of the cells to specific PMPMEase inhibitor altered F‐actin organization and induced apoptosis with EC50 of 3.0 μg/ml for A549 and 9.6 μg/ml for H460 cells. The PMPMEase overexpression and hyperactivity in lung cancer and the apoptosis resulting from its inhibition is a strong indication of its role in lung cancer progression. This implies that PMPMEase would be a strong candidate biomarker for diagnosis and target for therapy in lung cancer.