title: PME-1 modulates protein phosphatase 2A activity to promote the malignant phenotype of endometrial cancer cells.
abstract: Protein phosphatase 2A (PP2A) negatively regulates tumorigenic signaling pathways, in part, by supporting the function of tumor suppressors like p53. The PP2A methylesterase PME-1 limits the activity of PP2A by demethylating its catalytic subunit. Here, we report the finding that PME-1 overexpression correlates with increased cell proliferation and invasive phenotypes in endometrial adenocarcinoma cells, where it helps maintain activated ERK and Akt by inhibiting PP2A. We obtained evidence that PME-1 could bind and regulate protein phosphatase 4 (PP4), a tumor-promoting protein, but not the related protein phosphatase 6 (PP6). When the PP2A, PP4, or PP6 catalytic subunits were overexpressed, inhibiting PME-1 was sufficient to limit cell proliferation. In clinical specimens of endometrial adenocarcinoma, PME-1 levels were increased and we found that PME-1 overexpression was sufficient to drive tumor growth in a xenograft model of the disease. Our findings identify PME-1 as a modifier of malignant development and suggest its candidacy as a diagnostic marker and as a therapeutic target in endometrial cancer.
authors.affiliation: Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, a Member of the Genesis Biotechnology Group, LLC, Hamilton, New Jersey.
authors.forename: Ewa
authors.initials: E
authors.lastname: Wandzioch
authors.affiliation: Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, a Member of the Genesis Biotechnology Group, LLC, Hamilton, New Jersey.
authors.forename: Michelle
authors.initials: M
authors.lastname: Pusey
authors.affiliation: Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, a Member of the Genesis Biotechnology Group, LLC, Hamilton, New Jersey.
authors.forename: Amy
authors.initials: A
authors.lastname: Werda
authors.affiliation: Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, a Member of the Genesis Biotechnology Group, LLC, Hamilton, New Jersey.
authors.forename: Sophie
authors.initials: S
authors.lastname: Bail
authors.affiliation: Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, a Member of the Genesis Biotechnology Group, LLC, Hamilton, New Jersey.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Bhaskar
authors.affiliation: Pathology Division, Medical Diagnostic Laboratories LLC, a Member of the Genesis Biotechnology Group, LLC, Hamilton, New Jersey.
authors.forename: Mariya
authors.initials: M
authors.lastname: Nestor
authors.affiliation: Pathology Division, Medical Diagnostic Laboratories LLC, a Member of the Genesis Biotechnology Group, LLC, Hamilton, New Jersey.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, a Member of the Genesis Biotechnology Group, LLC, Hamilton, New Jersey. lrice@oncoveda.com.
authors.forename: Lyndi M
authors.initials: LM
authors.lastname: Rice
mesh_terms: D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism*; D048708:Cell Growth Processes / Q000502:physiology; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000235:genetics; D005260:Female; D064593:Heterografts; D006801:Humans; D008745:Methylation; D051379:Mice; D008819:Mice, Nude; D010641:Phenotype; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002265:Carboxylic Ester Hydrolases; C119357:protein phosphatase methylesterase-1; D054648:Protein Phosphatase 2