Augmenting cancer cell proteomics with cellular images – A semantic approach to understand focal adhesion

Bauer, Thomas Johann; Gombocz, Erich; Krüger, Marcus; Sahana, Jayashree; Corydon, Thomas J.; Bauer, Johann; Infanger, Manfred; Grimm, Daniela

doi:10.1016/j.jbi.2019.103320

Cited by 4 publications

(9 citation statements)

References 75 publications

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“…Figure 3 shows the interaction partners of the membrane-inserted proteins selected. They include a number of proteins, SPP1, MSN, FAS, CAV2, RAC1, SRC, EGFR, TLN1, ACTN1, PXN, PLEC, PTK2 and KDR, which emerged in our earlier studies as important players in transducing the signals of cell adhesion to the cytoskeleton [5,6,45,54,101,102]. Table 1.…”

Section: Interaction Of Sialylated Proteinsmentioning

confidence: 99%

“…Entities labeled by * have already been mentioned in ref. [6] or [45]. They are included for comparison and completion purposes because they influence the sialylation of adhesion proteins.…”

Section: Enzymes Responsible For the Status Of Adhesion Proteinsmentioning

confidence: 99%

“…A change of the conformation has an influence on the binding to extracellular matrix proteins or to extracellular domains of surface proteins of other cells. It could also give different signals to the cell interior with direction towards the cell nucleus [45].…”

Section: Biochemical and Biophysical Effects Of Sas Present On Extracmentioning

confidence: 99%

“…To create a semantic network, harmonize the content from multiple resources, and allow for graphical querying and reasoning, experimental data were imported to establish an initial resource description framework (RDF) knowledge base using KE (Melissa Informatics, Berkeley, CA, USA-former IO Informatics). This tool allows one to create, merge, and/or align semantic knowledge bases (SKB) in the form of RDF serializations as files or in backend databases and to configure and connect them to public semantic protocol and RDF query language (SPARQL) endpoints for query and import [20,[43][44][45]. Its import functions provide abilities for nomenclature alignment, to set or automate reification IDs for blank nodes, and to establish mapping for spreadsheets or XML datasets.…”

Section: Creation Of a Semantic Networkmentioning

confidence: 99%

“…UniProt content was queried for each of the proteins using its SPARQL endpoint [43,44,141]. This added functional, cellular location, chromosomal, and interaction properties to augment the information on the enzymes and reported protein functions [45,142]. The information collected was used to retrieve content from the Entréz resources OMIM, Protein, PubMed, and Biosystems ( Figure 6), as well as from dbPTM, GlyGen, Rhea, and Atlas of Genetics and Cytogenetics [20,143] by means of graphical queries and their result imports (Figure 4).…”

Section: Creation Of a Semantic Networkmentioning

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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Section: Interaction Of Sialylated Proteinsmentioning

confidence: 99%

Section: Enzymes Responsible For the Status Of Adhesion Proteinsmentioning

confidence: 99%

Section: Biochemical and Biophysical Effects Of Sas Present On Extracmentioning

confidence: 99%

Section: Creation Of a Semantic Networkmentioning

confidence: 99%

Section: Creation Of a Semantic Networkmentioning

confidence: 99%

See 3 more Smart Citations

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

Bauer

Gombocz²,

Wehland

et al. 2020

IJMS

Self Cite

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Interaction Network Provides Clues on the Role of BCAR1 in Cellular Response to Changes in Gravity

Bauer¹,

Gombocz²,

Schulz

et al. 2021

Computation

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When culturing cells in space or under altered gravity conditions on Earth to investigate the impact of gravity, their adhesion and organoid formation capabilities change. In search of a target where the alteration of gravity force could have this impact, we investigated p130cas/BCAR1 and its interactions more thoroughly, particularly as its activity is sensitive to applied forces. This protein is well characterized regarding its role in growth stimulation and adhesion processes. To better understand BCAR1′s force-dependent scaffolding of other proteins, we studied its interactions with proteins we had detected by proteome analyses of MCF-7 breast cancer and FTC-133 thyroid cancer cells, which are both sensitive to exposure to microgravity and express BCAR1. Using linked open data resources and our experiments, we collected comprehensive information to establish a semantic knowledgebase and analyzed identified proteins belonging to signaling pathways and their networks. The results show that the force-dependent phosphorylation and scaffolding of BCAR1 influence the structure, function, and degradation of intracellular proteins as well as the growth, adhesion and apoptosis of cells similarly to exposure of whole cells to altered gravity. As BCAR1 evidently plays a significant role in cell responses to gravity changes, this study reveals a clear path to future research performing phosphorylation experiments on BCAR1.

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Simulated Microgravity Influences VEGF, MAPK, and PAM Signaling in Prostate Cancer Cells

Hybel

Dietrichs

Sahana

et al. 2020

IJMS

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Prostate cancer is one of the leading causes of cancer mortality in men worldwide. An unusual but unique environment for studying tumor cell processes is provided by microgravity, either in space or simulated by ground-based devices like a random positioning machine (RPM). In this study, prostate adenocarcinoma-derived PC-3 cells were cultivated on an RPM for time periods of 3 and 5 days. We investigated the genes associated with the cytoskeleton, focal adhesions, extracellular matrix, growth, survival, angiogenesis, and metastasis. The gene expression of signaling factors of the vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK), and PI3K/AKT/mTOR (PAM) pathways was investigated using qPCR. We performed immunofluorescence to study the cytoskeleton, histological staining to examine the morphology, and a time-resolved immunofluorometric assay to analyze the cell culture supernatants. When PC-3 cells were exposed to simulated microgravity (s-µg), some cells remained growing as adherent cells (AD), while most cells detached from the cell culture flask bottom and formed multicellular spheroids (MCS). After 3-day RPM exposure, PC-3 cells revealed significant downregulation of the VEGF, SRC1, AKT, MTOR, and COL1A1 gene expression in MCS, whereas FLT1, RAF1, MEK1, ERK1, FAK1, RICTOR, ACTB, TUBB, and TLN1 mRNAs were not significantly changed. ERK2 and TLN1 were elevated in AD, and FLK1, LAMA3, COL4A5, FN1, VCL, CDH1, and NGAL mRNAs were significantly upregulated in AD and MCS after 3 days. After a 5-day culture in s-µg, the PC-3 cells showed significant downregulations of VEGF mRNA in AD and MCS, and FN1, CDH1, and LAMA3 in AD and SCR1 in MCS. In addition, we measured significant upregulations in FLT1, AKT, ERK1, ERK2, LCN2, COL1A1, TUBB, and VCL mRNAs in AD and MCS, and increases in FLK1, FN1, and COL4A5 in MCS as well as LAMB2, CDH1, RAF1, MEK1, SRC1, and MTOR mRNAs in AD. FAK1 and RICTOR were not altered by s-µg. In parallel, the secretion rate of VEGFA and NGAL proteins decreased. Cytoskeletal alterations (F-actin) were visible, as well as a deposition of collagen in the MCS. In conclusion, RPM-exposure of PC-3 cells induced changes in their morphology, cytoskeleton, and extracellular matrix protein synthesis, as well as in their focal adhesion complex and growth behavior. The significant upregulation of genes belonging to the PAM pathway indicated their involvement in the cellular changes occurring in microgravity.

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Augmenting cancer cell proteomics with cellular images – A semantic approach to understand focal adhesion

Cited by 4 publications

References 75 publications

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

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

Interaction Network Provides Clues on the Role of BCAR1 in Cellular Response to Changes in Gravity

Simulated Microgravity Influences VEGF, MAPK, and PAM Signaling in Prostate Cancer Cells

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