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Role of Hexosamine Biosynthetic Pathway on Cancer Stem Cells: Connecting Nutrient Sensing to Cancer Cell Plasticity
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Role of Hexosamine Biosynthetic Pathway on Cancer Stem Cells: Connecting Nutrient Sensing to Cancer Cell Plasticity

Giang Le Minh and Mauricio J. Reginato
Reference Module in Biomedical Research
2015

Abstract

Cancer stem cell Hexosamine biosynthetic pathway O-GlcNAc transferase O-GlcNAcylation Tumor-initiating cell
Cancer stem cells (CSCs) make up part of the heterogenous tumor bulk that plays a critical role in tumor cell growth and metastasis. Similar to adult stem cells, CSCs are capable of self-renewing and differentiating, resulting in bulk tumor growth, metastases and therapeutic resistance. The functions of CSCs are regulated by numerous pathways. One pathway that is emerging as an important regulator of CSCs is the hexosamine biosynthetic pathway (HBP), which can serve as a sensor between cell metabolism and signaling pathways. Key enzymes regulating the HBP and its final product UDP-N-acetylglucosamine (UDP-GlcNAc) have been found to be altered in many types of cancers. The HBP regulates complex glycosylation of membrane and secreted proteins as well as glycosylation of nuclear and cytoplasmic proteins via O-GlcNAcylation. Similar to HBP, O-GlcNAcylation has been reported to play a key role in both cancer cells and stem cells. In this review, we discuss the emerging role of HBP and O-GlcNAcylation in regulating the function of CSCs and cell plasticity, and the potential of the HBP in therapeutic approaches in targeting cancer stem cells.

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