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Silencing of Carboxypeptidase E Inhibits Cell Proliferation, Tumorigenicity, and Metastasis of Osteosarcoma Cells

Overview
Publisher Dove Medical Press
Specialty Oncology
Date 2016 Jun 9
PMID 27274275
Citations 13
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Abstract

Carboxypeptidase E (CPE), a prohormone processing enzyme, has been implicated in the progression of multiple malignancies. However, the biological role and molecular mechanisms of CPE in osteosarcoma remain elusive. In this study, we assessed the effects of CPE on cell proliferation, tumorigenicity, migration, and invasion in osteosarcoma. Our results showed that silencing of CPE significantly inhibited cell proliferation, caused cell cycle arrest at G0/G1 phase, decreased the expression levels of cell cycle protein, cyclin D1, and inhibited tumorigenicity in vivo. Additionally, CPE downregulation repressed the migratory and invasive capacities of osteosarcoma cells in vitro. Furthermore, overexpression of CPE-ΔN (a splice variant of CPE) enhanced the cell growth, migration, and invasion of osteosarcoma cells. It is possible that both CPE forms are involved in the tumorigenesis and development of osteosarcoma, and therefore CPE may provide a promising biological target for osteosarcoma therapy.

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References
1.
Jirawatnotai S, Hu Y, Michowski W, Elias J, Becks L, Bienvenu F . A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. Nature. 2011; 474(7350):230-4. PMC: 3134411. DOI: 10.1038/nature10155. View

2.
Fricker L, Snyder S . Purification and characterization of enkephalin convertase, an enkephalin-synthesizing carboxypeptidase. J Biol Chem. 1983; 258(18):10950-5. View

3.
Cawley N, Zhou J, Hill J, Abebe D, Romboz S, Yanik T . The carboxypeptidase E knockout mouse exhibits endocrinological and behavioral deficits. Endocrinology. 2004; 145(12):5807-19. DOI: 10.1210/en.2004-0847. View

4.
Murthy S, Dupart E, Al-Sweel N, Chen A, Cawley N, Loh Y . Carboxypeptidase E promotes cancer cell survival, but inhibits migration and invasion. Cancer Lett. 2013; 341(2):204-13. PMC: 3825807. DOI: 10.1016/j.canlet.2013.08.011. View

5.
Cawley N, Wetsel W, Murthy S, Park J, Pacak K, Loh Y . New roles of carboxypeptidase E in endocrine and neural function and cancer. Endocr Rev. 2012; 33(2):216-53. PMC: 3365851. DOI: 10.1210/er.2011-1039. View