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O‐GlcNAcylation Modifies the Metastatic Properties of Prostate Cancer Cells
Author(s) -
Liu Xin,
mooney Steven,
Hart Gerald
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.717.2
Subject(s) - lncap , prostate cancer , cancer , cytoplasm , metastasis , cancer cell , cancer research , blot , biology , prostate , cell culture , cell growth , microbiology and biotechnology , chemistry , biochemistry , genetics , gene
O‐GlcNAc is a ubiquitous and dynamic post‐translational modification that occurs on serine/threonine residues of nuclear and cytoplasmic proteins. It is regulated by O‐GlcNAc transferase, which attaches O‐GlcNAc to proteins and O‐GlcNAcase, which removes O‐GlcNAc.It serves as a nutrient sensor to regulate virtually all cellular processes, as well as playing roles in various diseases, including Alzheimer's disease, diabetes and cancer. The roles of O‐GlcNAc in the regulation of prostate cancer remain unclear. Herein, we investigate how the regulation of O‐GlcNAc may drive prostate cancer progression using normal prostate epithelial cells and prostate cancer cell lines as models, and human tissue arrays. Using western blotting, we demonstrate that O‐GlcNAc, OGT and OGA are highly elevated in LNCaP and PC‐3 when compared to PrEC. LNCaP exhibited the highest levels of O‐GlcNAc, OGT and OGA. OGT and OGA are differentially localized in lines with different metastatic properties. Additionally, 2D gel electrophoresis reveals significant differences in O‐GlcNAcylated protein profiles among the three cell lines. In order to address how O‐GlcNAc affects the biological properties of these cancer cells, including shapes, proliferation, invasion and metastasis, several assays were used. The result of soft agar assays indicates that cycling of O‐GlcNAc in cells influence the anchorage independent growth of prostate cancer. Interestingly, analyses of human tissues indicate that there is a field effect in O‐GlcNAc expression with higher levels in the cytoplasm of cancer and the cytoplasm of benign tissue in close proximity to the cancer.