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Medicine and Health Sciences Commons

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Medical Sciences

All ETDs from UAB

2019

Glycosylation

Articles 1 - 3 of 3

Full-Text Articles in Medicine and Health Sciences

St6gal-I Mediated Sialylation Promotes Pancreatic Ductal Adenocarcinoma Progression And Chemoresistance, Asmi Chakraborty Jan 2019

St6gal-I Mediated Sialylation Promotes Pancreatic Ductal Adenocarcinoma Progression And Chemoresistance, Asmi Chakraborty

All ETDs from UAB

ST6Gal-I adds α2-6 sialic acids to select N-glycosylated cell surface receptors, thereby modulating receptor function and intracellular signaling. ST6Gal-I is upregulated in various carcinomas and confers cancer stem cell (CSC) properties evidenced by tumorspheroid growth, chemoresistance and tumor initiating potential. In pancreatic ductal adenocarcinoma (PDAC), ST6Gal-I conferred gemcitabine resistance by abrogating DNA damage and altering expression levels of gemcitabine metabolism genes. Further, ST6Gal-I promoted resistance to chronic gemcitabine treatment. Additionally, metastatic clones of a PDAC cell line had increased ST6Gal-I expression and ST6Gal-I knockdown enhanced gemcitabine sensitivity. To investigate the physiological consequences of ST6Gal-I in PDAC, murine models were used. …


Receptor Sialylation By St6gal-I Promotes Tumor Progression By Enhancing Tumor Cell Survival And Epithelial To Mesenchymal Transition, Colleen Maeve Britain Jan 2019

Receptor Sialylation By St6gal-I Promotes Tumor Progression By Enhancing Tumor Cell Survival And Epithelial To Mesenchymal Transition, Colleen Maeve Britain

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The upregulation of a certain subset of glycosyltransferases was an early marker for cancer development. Specifically, ST6Gal-I, which adds an α2-6 linked sialic acid to N-glycans on proteins bound for the plasma membrane or secretion, is selectively upregulated upon malignant transformation. Our laboratory has shown that ST6Gal-I is implicated in many facets of tumor biology and is an important mediator of tumorigenesis. For example, ST6Gal-I activity promotes the survival of cells when challenged with hypoxia, FasL, or TNFα, confers resistance to chemotherapeutics, enhances tumor cell migration and invasion, and fosters a cancer stem cell phenotype. The work presented in this …


The Role Of The St6gal-I Sialyltrasferase In Protecting Tumor Cells From Hypoxic Stress, Robert Brent Jones Jan 2019

The Role Of The St6gal-I Sialyltrasferase In Protecting Tumor Cells From Hypoxic Stress, Robert Brent Jones

All ETDs from UAB

An emerging concept in cancer biology is that surface glycosylation can play important roles in the regulation of cancer development and progression. Our group and others have shown that ST6Gal-I, a sialyltransferase that adds α2-6-linked sialic acids to N-glycosylated proteins, is upregulated in many cancers. Furthermore, data has indicated that ST6Gal-I acts as a pro-survival factor in a variety of settings, including resistance to chemotherapeutic drugs, radiotherapy resistance, and serum deprivation. The work presented in this dissertation adds to this understanding of ST6Gal-I’s role as a potent pro-survival factor and explores ST6Gal-I’s function in aiding tumor cells to survive hypoxic …