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The Bellis laboratory is studying the role of receptor glycosylation in regulating tumor cell signaling and phenotype. In particular, we are focused on the ST6Gal-I sialyltransferase, which adds α2-6-linked sialic acids to N-glycosylated proteins. One of our primary research goals has been to identify specific substrates for ST6Gal-I and define the effects of variant sialylation on the structure and function of this cohort. These studies have shown that α2-6 sialylation alters the conformation of the β integrin, driving cell migration and invasion, whereas α2-6 sialylation of the Fas and TNFR1 death receptors prevents receptor internalization, leading to a block in apoptosis. The net effect of elevated tumor cell sialylation is to promote an invasive, apoptosis-resistant cell phenotype. Furthermore, ST6Gal-I imparts all of the hallmark characteristics of a cancer stem cell (CSC) including self-renewal potential, tumor-initiating capability, and resistance to a wide array of cytotoxic stressors including hypoxia, serum-deficiency, chemotherapy drugs and inflammatory stimuli. Furthermore, our group developed the first ST6Gal-I knock-in mouse model and determined that forced ST6Gal-I overexpression drives tumorigenesis in chemically-induced and genetic models of adenocarcinoma. Finally, we have shown that human pancreatic and ovarian cancer tissues have upregulated ST6Gal-I expression, and high ST6Gal-I expression correlates with reduced progression-free and overall patient survival.
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NEOPLASIA (2024): 100984-100984
Aubrey L. Miller,Samuel C. Fehling, Rebecca B. Vance,Dongquan Chen, Eric Josh Brown, M. Iqbal Hossain, Eric O. Heard,Shaida Andrabi,Hengbin Wang,Eddy S. Yang,Donald J. Buchsbaum, Robert C.A.M. van Waardenburg,
Cancer Letters (2024): 216919-216919
Joelle Saad, G. C. Sajina,Travis Nemkov,Kaysaw Tuy,Sam Gary,Victor Darley-Usmar,Susan Bellis,Anita Hjelmeland
GLYCOBIOLOGYno. 11 (2023): 1046-1046
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Amanda F. Swindall, Angelina I. Londoño-Joshi,Matthew J. Schultz,Naomi Fineberg,Donald J. Buchsbaum,Susan L. Bellis
crossref(2023)
GLYCOBIOLOGYno. 11 (2023): 976-977
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Cancer Researchno. 7_Supplement (2023): 336-336
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CANCER RESEARCHno. 7 (2023)
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