No abstract

Background O‐N‐acetylglucosaminylation (O‐GlcNAcylation) is unique type of protein glycosylation. The nature of O‐GlcNAcylation and its interplay with O‐phosphorphylation make this modification a regulator of many cellular functions. Hyper‐O‐GlcNAcylation is a general feature of many cancers. Objective: To determine the tumorgenic potential of O‐GlcNAcylation in cervical cancer cells through the inhibition of O‐linked N‐acetylglucosamine transferase (OGT). Methods: The OGT inhibitor, Alloxan, was used to block global O‐GlcNAcylation of immortalized cervical cancer cells (SiHa cells). Tumorigenic potential was assessed by measurement of cell proliferation and cytokine resistance. Proteomic analysis of control and Alloxan treated samples were compared by LTQ‐Orbitrap. Results: Inhibition of O‐GlcNAcylation in SiHa cells inhibited cell growth as assessed by cell proliferation assays. Total number of generations, multiplication rate, and generation time for control and Alloxan‐treated cells was 2.6 vs. 0.68 generations, 0.31 vs. 0.08 doublings per day, and 2.27 vs. 8.76 days, respectively (n=2 independent experiments).The loss of O‐GlcNAcylation also increased the susceptibility of the SiHa cells to cytokine‐induced death (P<0.05, n=3). Initial results of proteomic analysis indicated an up‐regulation of apoptotic proteins (e.g., programmed cell death protein 5), and a down‐regulation of anti‐apoptotic proteins (eukaryotic initiation factor 4) in Alloxan‐treated cells. Conclusion Global O‐GlcNAcylation is a critical regulator of cervical cancer cell proliferation, and apoptotic resistance. Support: The COLSA Karabelas fund and the NSF Graduate Research Fellowship Program.

No abstract