Aberrant glycosylation in hypoxic conditions: regulation and immune interactions

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B977
Abstract ID: 7861

Presenting Author:
Sepideh Dolatshahi , Assistant Professor of Biomedical Engineering at Univ. of Virginia Sch. of Med.

Abstract:

Glycosylation, the post-translational addition of glycans to proteins, plays a key role in modulating intra- and intercellular signaling pathways. Glycans have been utilized as biomarkers for early diagnosis and linked to tumor progression, metastasis, and patient survival. Sialylation and core fucosylation are elevated in non-small cell lung cancers (NSCLC) and melanoma as compared to normal tissue and as stage progresses. The Golgi apparatus is the protein processing of the cell; hypoxia-induced structural disruptions affect patterns of glycosylation. However, the functional consequences of Golgi fragmentation and aberrant glycosylation in the tumor-immune interactions and the underlying regulatory mechanisms remain understudied.

Our analysis of publicly available transcriptomics datasets suggests that while NSCLC and melanoma exhibit similar patterns of glycosylation and hypoxia, differences were observed in their underlying regulatory mechanisms, including the potential involvement of Golgi structure in regulating the observed aberrant glycosylation. Hypoxia pathway activity was negatively associated with expression of GOLPH3, GOLGA1, COG4, and PAQR3 –Golgi proteins that promote fragmentation; the trend was opposite in melanoma. Through in vitro experiments, we characterized the mechanisms of hypoxia-induced glycan abnormalities. Analysis of single cell transcriptomics data from humans uncovered tumor glycans modulation of the tumor-immune interaction networks.