title: Polyisoprenylated methylated protein methyl esterase overexpression and hyperactivity promotes lung cancer progression.
abstract: The involvement of hyperactive polyisoprenylated proteins in cancers has stimulated the search for drugs to target and suppress their excessive activities. Polyisoprenylated methylated protein methyl esterase (PMPMEase) inhibition has been shown to modulate polyisoprenylated protein function. For PMPMEase inhibition to be effective against cancers, polyisoprenylated proteins, the signaling pathways they mediate and/or PMPMEase must be overexpressed, hyperactive and be involved in at least some cases of cancer. PMPMEase activity in lung cancer cells and its expression in lung cancer cells and cancer tissues were investigated. PMPMEase was found to be overexpressed and significantly more active in lung cancer A549 and H460 cells than in normal lung fibroblasts. In a tissue microarray study, PMPMEase immunoreactivity was found to be significantly higher in lung cancer tissues compared to the normal controls (p < 0.0001). The mean scores ± SEM were 118.8 ± 7.7 (normal), 232.1 ± 25.1 (small-cell lung carcinomas), 352.1 ± 9.4 (squamous cell carcinomas), 311.7 ± 9.8 (adenocarcinomas), 350.0 ± 24.2 (papillary adenocarcinomas), 334.7 ± 30.1 (adenosquamous carcinomas), 321.9 ± 39.7 (bronchioloalveolar carcinomas), and 331.3 ± 85.0 (large-cell carcinomas). Treatment of lung cancer cells with L-28, a specific PMPMEase inhibitor, resulted in concentration-dependent cell death (EC50 of 8.5 μM for A549 and 2.8 μM for H460 cells). PMPMEase inhibition disrupted actin filament assembly, significantly inhibited cell migration and altered the transcription of cancer-related genes. These results indicate that elevated PMPMEase activity spur cell growth and migration, implying the possible use of PMPMEase as a protein biomarker and drug target for lung cancer.
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University Tallahassee, Florida 32307, USA.
authors.forename: Felix
authors.initials: F
authors.lastname: Amissah
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University Tallahassee, Florida 32307, USA.
authors.forename: Randolph
authors.initials: R
authors.lastname: Duverna
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University Tallahassee, Florida 32307, USA.
authors.forename: Byron J
authors.initials: BJ
authors.lastname: Aguilar
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University Tallahassee, Florida 32307, USA.
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Poku
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University Tallahassee, Florida 32307, USA.
authors.forename: Gebre-Egziabher
authors.initials: GE
authors.lastname: Kiros
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University Tallahassee, Florida 32307, USA.
authors.forename: Nazarius S
authors.initials: NS
authors.lastname: Lamango
keywords: Polyisoprenylation; Ras; esterase; isoprenylation; lung cancer; methylation; monomeric G-proteins; nanostring