Download Metastasis, the malignant stage in cancer development is

Changes in sugar metabolism are well documented in diabetes, neurodegenerative,
and cancer diseases. This phenomenon is conjugated to impaired protein
glycosylation. It has been reported recently that the unique -N-acetyl glucose amine
proteins modification is altered in diabetes and Alzheimer diseases.
The current study hypothesize that O-GlcNAcylation is altered during cancer
metastasis which leads to dysregulation of the modified proteins and thus contribute
to the metastasis phenotype. Proteomics analysis of nuclear proteins showed, that
GlcNAcylation profile is different between the metastatic and nonmetastatic
colorectal cancer clones. Interestingly, GlcNAcylation of several proteins is elevated
in the metastatic clone while the GlcNAcylation of others is elevated in the
nonmetastatic clones. Metastatic and metastatic clones treatments with glucose,
GlcNAc and streptozotocin—an inhibitor of O-GlcNAcase— leads to the elevation in
total proteins GlcNAcylation. Remarkably, several proteins possess GlcNAcylation
only after cancer cell treatments. Glucose and GlcNAc treatments lead to reduced
viability of the metastatic and nonmetastatic cell cultures in dose response manner.
surprisingly, the metastatic clone renders higher sensitivity to those treatments.
STZ treatment in combination with GlcNAc is additive and more effective than STZ
alone. These results shed lights on GlcNAcylation involvement in cancer metastasis
and pave the way for comprehensive elucidation.