Carboxypeptidase E-∆N Promotes Proliferation and Invasion of Pancreatic Cancer Cells via Upregulation of CXCR2 Gene Expression

International Journal of Molecular Sciences. 2019;20(22):5725 DOI 10.3390/ijms20225725

 

Journal Homepage

Journal Title: International Journal of Molecular Sciences

ISSN: 1661-6596 (Print); 1422-0067 (Online)

Publisher: MDPI AG

LCC Subject Category: Science: Biology (General) | Science: Chemistry

Country of publisher: Switzerland

Language of fulltext: English

Full-text formats available: PDF, HTML, XML

 

AUTHORS


Sangeetha Hareendran (Section on Cellular Neurobiology, <i>Eunice Kennedy Shriver</i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA)

Xuyu Yang (Section on Cellular Neurobiology, <i>Eunice Kennedy Shriver</i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA)

Hong Lou (Section on Cellular Neurobiology, <i>Eunice Kennedy Shriver</i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA)

Lan Xiao (Section on Cellular Neurobiology, <i>Eunice Kennedy Shriver</i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA)

Y. Peng Loh (Section on Cellular Neurobiology, <i>Eunice Kennedy Shriver</i> National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA)

EDITORIAL INFORMATION

Blind peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 11 weeks

 

Abstract | Full Text

Pancreatic cancer is one of the leading causes of cancer-related mortality worldwide. The molecular basis for the pathogenesis of this disease remains elusive. In this study, we have investigated the role of wild-type Carboxypeptidase E (CPE-WT) and a 40 kDa N-terminal truncated isoform, CPE-&#916;N in promoting proliferation and invasion of Panc-1 cells, a pancreatic cancer cell line. Both CPE-WT and CPE-&#916;N were expressed in Panc-1 and BXPC-3 pancreatic cancer cells. Immunocytochemical studies revealed that in CPE transfected Panc-1 cells, CPE-&#916;N was found primarily in the nucleus, whereas CPE-WT was present exclusively in the cytoplasm as puncta, characteristic of secretory vesicles. Endogenous CPE-WT was secreted into the media. Overexpression of CPE-&#916;N in Panc-1 cells resulted in enhancement of proliferation and invasion of these cells, as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell proliferation assay and Matrigel invasion assay, respectively. In contrast, the expression of CPE-WT protein at comparable levels to CPE-&#916;N in Panc-1 cells resulted in promotion of proliferation but not invasion. Importantly, there was an upregulation of the expression of <i>CXCR2</i> mRNA and protein in Panc-1 cells overexpressing CPE-&#916;N, and these cells exhibited significant increase in proliferation in a CXCR2-dependent manner. Thus, CPE-&#916;N may play an important role in promoting pancreatic cancer growth and malignancy through upregulating the expression of the metastasis-related gene, <i>CXCR2</i>.