Inhibition of protein methylesterase 1 decreased cancerous phenotypes in endometrial adenocarcinoma cell lines and xenograft tumor models

  • Tumour Biol. 2016 Sep;37(9):11835-11842. doi: 10.1007/s13277-016-5036-8.
Michelle Pusey  1 ,  Sophie Bail  1 ,  Yan Xu  2 ,  Olesia Buiakova  2 ,  Mariya Nestor  3 ,  Jing-Jing Yang  3 ,  Lyndi M Rice  4
Affiliations
  • 1. Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, 1000 Waterview Drive, Room 345, Hamilton, NJ, 08691, USA.
  • 2. Invivotek, LLC, 16 Black Forest Road, Hamilton, NJ, 08691, USA.
  • 3. Pathology Department, Members of Genesis Biotechnology Group, LLC, Medical Diagnostic Laboratories LLC, 2439 Kuser Road, Hamilton, NJ, 08690, USA.
  • 4. Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLC, 1000 Waterview Drive, Room 345, Hamilton, NJ, 08691, USA. [email protected].
PMID: 27048286 DOI: 10.1007/s13277-016-5036-8
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.

Keywords
ABL-127; Endometrial cancer; PME-1; PP2A.
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