title: Inhibition of protein methylesterase 1 decreased cancerous phenotypes in endometrial adenocarcinoma cell lines and xenograft tumor models.
abstract: Protein methylesterase 1 (PME-1) promotes cancerous phenotypes through the demethylation and inactivation of protein phosphatase 2A. We previously demonstrated that PME-1 overexpression promotes Akt, ERK, and may promote Wnt signaling and increases tumor burden in a xenograft model of endometrial cancer. Here, we show that covalent PME-1 inhibitors decrease cell proliferation and invasive growth in vitro but have no effect in vivo at the concentrations tested; however, depletion of PME-1 with shRNA in an endometrial cancer xenograft model significantly reduced tumor growth. Thus, discovery of more potent PME-1 inhibitors may be beneficial for the treatment of endometrial cancer.
authors.affiliation: Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, 1000 Waterview Drive, Room 345, Hamilton, NJ, 08691, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Pusey
authors.affiliation: Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, 1000 Waterview Drive, Room 345, Hamilton, NJ, 08691, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Bail
authors.affiliation: Invivotek, LLC, 16 Black Forest Road, Hamilton, NJ, 08691, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Invivotek, LLC, 16 Black Forest Road, Hamilton, NJ, 08691, USA.
authors.forename: Olesia
authors.initials: O
authors.lastname: Buiakova
authors.affiliation: Pathology Department, Members of Genesis Biotechnology Group, LLC, Medical Diagnostic Laboratories LLC, 2439 Kuser Road, Hamilton, NJ, 08690, USA.
authors.forename: Mariya
authors.initials: M
authors.lastname: Nestor
authors.affiliation: Pathology Department, Members of Genesis Biotechnology Group, LLC, Medical Diagnostic Laboratories LLC, 2439 Kuser Road, Hamilton, NJ, 08690, USA.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, 1000 Waterview Drive, Room 345, Hamilton, NJ, 08691, USA. lrice@oncoveda.com.
authors.forename: Lyndi M
authors.initials: LM
authors.lastname: Rice
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D010641:Phenotype; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: C000602511:eicosanoyl-5-hydroxytryptamide; D012701:Serotonin; D002265:Carboxylic Ester Hydrolases; C119357:protein phosphatase methylesterase-1
keywords: ABL-127; Endometrial cancer; PME-1; PP2A