TY - JOUR

T1 - Insight in Adhesion Protein Sialylation and Microgravity Dependent Cell Adhesion-An Omics Network Approach

AU - Bauer, Thomas J

AU - Gombocz, Erich

AU - Wehland, Markus

AU - Bauer, Johann

AU - Infanger, Manfred

AU - Grimm, Daniela

PY - 2020

Y1 - 2020

N2 - The adhesion behavior of human tissue cells changes in vitro, when gravity forces affecting these cells are modified. To understand the mechanisms underlying these changes, proteins involved in cell-cell or cell-extracellular matrix adhesion, their expression, accumulation, localization, and posttranslational modification (PTM) regarding changes during exposure to microgravity were investigated. As the sialylation of adhesion proteins is influencing cell adhesion on Earth in vitro and in vivo, we analyzed the sialylation of cell adhesion molecules detected by omics studies on cells, which change their adhesion behavior when exposed to microgravity. Using a knowledge graph created from experimental omics data and semantic searches across several reference databases, we studied the sialylation of adhesion proteins glycosylated at their extracellular domains with regards to its sensitivity to microgravity. This way, experimental omics data networked with the current knowledge about the binding of sialic acids to cell adhesion proteins, its regulation, and interactions in between those proteins provided insights into the mechanisms behind our experimental findings, suggesting that balancing the sialylation against the de-sialylation of the terminal ends of the adhesion proteins' glycans influences their binding activity. This sheds light on the transition from two- to three-dimensional growth observed in microgravity, mirroring cell migration and cancer metastasis in vivo.

AB - The adhesion behavior of human tissue cells changes in vitro, when gravity forces affecting these cells are modified. To understand the mechanisms underlying these changes, proteins involved in cell-cell or cell-extracellular matrix adhesion, their expression, accumulation, localization, and posttranslational modification (PTM) regarding changes during exposure to microgravity were investigated. As the sialylation of adhesion proteins is influencing cell adhesion on Earth in vitro and in vivo, we analyzed the sialylation of cell adhesion molecules detected by omics studies on cells, which change their adhesion behavior when exposed to microgravity. Using a knowledge graph created from experimental omics data and semantic searches across several reference databases, we studied the sialylation of adhesion proteins glycosylated at their extracellular domains with regards to its sensitivity to microgravity. This way, experimental omics data networked with the current knowledge about the binding of sialic acids to cell adhesion proteins, its regulation, and interactions in between those proteins provided insights into the mechanisms behind our experimental findings, suggesting that balancing the sialylation against the de-sialylation of the terminal ends of the adhesion proteins' glycans influences their binding activity. This sheds light on the transition from two- to three-dimensional growth observed in microgravity, mirroring cell migration and cancer metastasis in vivo.

KW - Cadherin

KW - Graphical SPARQL

KW - Integrin

KW - Linked open database

KW - Proteome

KW - Semantic knowledgebase

UR - http://www.scopus.com/inward/record.url?scp=85080997952&partnerID=8YFLogxK

U2 - 10.3390/ijms21051749

DO - 10.3390/ijms21051749

M3 - Journal article

C2 - 32143440

VL - 21

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 5

M1 - 1749

ER -