O-GlcNAcylation of HIF-1α Protein in Human Breast Cancer Cells

Dolsen, Joshua D. (2019) O-GlcNAcylation of HIF-1α Protein in Human Breast Cancer Cells. Undergraduate thesis, under the direction of Yu-Dong Zhou from Chemistry and Biochemistry, University of Mississippi.

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Abstract

Cancer is an insidious disease that, if not caught in time, can cause devastating effects on the human body, especially if it metastasizes. It is important to note that each cancer behaves and develops differently based on its location in the body and the cellular characteristics constitute the instance of the disease. However, the development of cancer can universally be characterized by the acquisition of different hallmark abilities that promote disease progression. Proteins known as hypoxia-inducible factors (HIFs) can influence progression through these hallmarks, but primarily provides cancer cells with the ability to alter its metabolism to survive and further progress in hypoxic conditions, which are common intratumorally. The HIF transcription factors are composed of two subunits, an ‘α’-subunit that is oxygen-regulated and a constitutively expressed ‘β’-subunit. Posttranslational modifications are a common form of regulation among cell types. Specifically, enhanced O-GlcNAcylation, the addition of O-linked β-N-acetylglucosamine (O-GlcNAc), has been observed to have implications in the progression of diseases, including breast cancer. The purpose of this research is to detect O-GlcNAcylation of HIF-1α protein, using the triple negative breast cancer MDA-MB-321-derived (MDA-MB-231 BoM) bone-specific organotropic subclone as an in vitro model.

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