Semantic Analysis of Posttranslational Modification of Proteins Accumulated in Thyroid Cancer Cells Exposed to Simulated Microgravity

Bauer, Johann; Wehland, Markus; Infanger, Manfred; Grimm, Daniela; Gombocz, Erich

doi:10.3390/ijms19082257

Cited by 22 publications

(28 citation statements)

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“…Experiments in µg contribute to drug discovery by providing an environment which is helpful to detect changes in gene expression and protein synthesis and secretion that occur during the progression from 2D to 3D growth and which might represent new targets for drug development against thyroid cancer. A couple of these proteins were found in follicular thyroid cancer cells by analyzing multiple pilot studies, performed in µg, with the help of semantic methods [31,32]. Some of these potential drugs, including DEX, were recently reviewed [33].…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone Inhibits Spheroid Formation of Thyroid Cancer Cells Exposed to Simulated Microgravity

Melnik

Sahana

Corydon

et al. 2020

Cells

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Detachment and the formation of spheroids under microgravity conditions can be observed with various types of intrinsically adherent human cells. In particular, for cancer cells this process mimics metastasis and may provide insights into cancer biology and progression that can be used to identify new drug/target combinations for future therapies. By using the synthetic glucocorticoid dexamethasone (DEX), we were able to suppress spheroid formation in a culture of follicular thyroid cancer (FTC)-133 cells that were exposed to altered gravity conditions on a random positioning machine. DEX inhibited the growth of three-dimensional cell aggregates in a dose-dependent manner. In the first approach, we analyzed the expression of several factors that are known to be involved in key processes of cancer progression such as autocrine signaling, proliferation, epithelial–mesenchymal transition, and anoikis. Wnt/β-catenin signaling and expression patterns of important genes in cancer cell growth and survival, which were further suggested to play a role in three-dimensional aggregation, such as NFKB2, VEGFA, CTGF, CAV1, BCL2(L1), or SNAI1, were clearly affected by DEX. Our data suggest the presence of a more complex regulation network of tumor spheroid formation involving additional signal pathways or individual key players that are also influenced by DEX.

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Section: Introductionmentioning

confidence: 99%

Dexamethasone Inhibits Spheroid Formation of Thyroid Cancer Cells Exposed to Simulated Microgravity

Melnik

Sahana

Corydon

et al. 2020

Cells

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“…SA is transferred from SA-CMP to a terminal galactose of an existing glycan (see: https://www.rhea-db.org/reaction?id=15907). [20]; Each LfQ value shown for the MCF-7 cells is an average value of the independent measurements of four equally prepared samples [6]. Entities labeled by * have already been mentioned in ref.…”

Section: Enzymes Responsible For the Status Of Adhesion Proteinsmentioning

confidence: 99%

“…The omics technology revealed changes of expression and/or accumulation of adhesion proteins under microgravity in AD and MCS cells as compared to control cells cultured under 1g-conditions [5,6]. Hence, additional information was collected about microgravity-dependent posttranslational modifications [20], including phosphorylation [9,21], ubiquitination [22,23], or isgylation [6,24], and about the intracellular translocation of adhesion proteins [25,26].…”

Section: Introductionmentioning

confidence: 99%

“…Posttranslational modification (PTM) is accomplished by enzymes such as kinases, phosphatases, or ligases [20][21][22][23][24]. In some types of PTM, carbohydrates are bound to reactive oxygens (O-glycan) or nitrogens (N-glycan) of a protein's amino acid side chains [27].…”

Section: Introductionmentioning

confidence: 99%

“…Carbohydrate units coupled directly to an amino acid can be determined by mass spectrometry [29]. The results of such analyses have been collected in overview databases such as the UniProt (https://www.uniprot.org/) or dbPTM databases (http://dbptm.mbc.edu.tw) [20]. However, very often this knowledge is not sufficient, because the biological effect of a protein-bound carbohydrate system is exerted by carbohydrate monomers located at the terminal end of a glycan system consisting of tens or even hundreds of carbohydrate monomers.…”

Section: Introductionmentioning

confidence: 99%

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

Bauer

Gombocz²,

Wehland

et al. 2020

IJMS

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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.

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Effects of rotary cell culture system‐simulated microgravity on the ultrastructure and biological behavior of human MDA‐MB‐231 breast cancer cells

Jiang

Chen

et al. 2019

Precision Radiation Oncology

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Objective: This study aimed to investigate changes in the ultrastructure, apoptosis, cycle progression, and migration ability of human MDA-MB-231 breast cancer cells under simulated microgravity conditions. Methods: MDA-MB-231 breast cancer cells were cultured in a rotary cell culture system bioreactor to simulate microgravity for 7 days. The cells were randomly divided into a simulated microgravity (SMG) group and normal gravity control (NG) group. Changes in apoptosis, ultrastructure, cell cycle, and migration ability were evaluated.Results: Transmission electron microscopy showed that cells in the SMG group had more secondary lysosomes than the NG groups. The flow cytometry assay showed that the proportion of apoptotic cells in the SMG group was significantly increased compared with the NG group; additionally, the median and interquartile spacing of the proportion of cells in the G0/G1 phase in the SMG group was lower than in the NG group, but the proportion of cells in the S phase was increased in the SMG group compared with the NG group. The transwell migration assay showed that cell migration in the SMG group was significantly reduced compared with the NG group. The expression of BCL-2 and MMP9 in the SMG group was decreased compared with the NG group, whereas the expression of cyclin D3 in the SMG group was increased. Conclusion: Simulated microgravity through rotary cell culture system had significant effects on human MDA-MB-231 breast cancer cells: the cell cycle and ultrastructure were impaired, apoptosis increased, migration ability decreased, and the expression of BCL-2, cyclin D3, and MMP9 were affected. K E Y W O R D S cell apoptosis, cell migration, cell ultrastructure, MDA-MB-231 breast cancer, simulated microgravity 1

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Semantic Analysis of Posttranslational Modification of Proteins Accumulated in Thyroid Cancer Cells Exposed to Simulated Microgravity

Cited by 22 publications

References 50 publications

Dexamethasone Inhibits Spheroid Formation of Thyroid Cancer Cells Exposed to Simulated Microgravity

Dexamethasone Inhibits Spheroid Formation of Thyroid Cancer Cells Exposed to Simulated Microgravity

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

Effects of rotary cell culture system‐simulated microgravity on the ultrastructure and biological behavior of human MDA‐MB‐231 breast cancer cells

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