Semantic Analysis of Posttranslational Modification of Proteins Accumulated in Thyroid Cancer Cells Exposed to Simulated Microgravity
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Published on: August 25, 2022
Johann Bauer1, Markus Wehland2, Manfred Infanger3
1Max-Planck-Institute for Biochemistry, 82152 Martinsried, Germany. jbauer@biochem.mpg.de.
Abstract:
When monolayers of tissue cancer cells of various origins are exposed to real or simulated microgravity, many cells leave the monolayer and assemble to three-dimensional (3D) aggregates (spheroids). In order to define the cellular machinery leading to this change in growth behavior of FTC-133 human thyroid cancer cells and MCF-7 breast cancer cells, we recently performed proteome analyses on these cell lines and determined the proteins' accumulation in monolayer cells grown under 1g-conditions as well as in the cells of spheroids assembled under simulated microgravity during three and 14 days, respectively. At that time, an influence of the increment or decrement of some of the more than 5000 proteins detected in each cell line was investigated. In this study, we focused on posttranslational modifications (PTMs) of proteins. For this purpose, we selected candidates from the list of the proteins detected in the two preceding proteome analyses, which showed significant accumulation in spheroid cells as compared to 1g monolayer cells. Then we searched for those PTMs of the selected proteins, which according to the literature have already been determined experimentally. Using the Semantic Protocol and RDF Query Language (SPARQL), various databases were examined. Most efficient was the search in the latest version of the dbPTM database. In total, we found 72 different classes of PTMs comprising mainly phosphorylation, glycosylation, ubiquitination and acetylation. Most interestingly, in 35 of the 69 proteins, N6 residues of lysine are modifiable.
Insights
Cancer cells in microgravity form 3D spheroids. This study identified 72 post-translational modifications (PTMs) in proteins, revealing key changes in cell behavior and potential therapeutic targets for cancer research.
Area of Science:
- Cell Biology
- Biochemistry
- Proteomics
Background:
- Cancer cells in microgravity transition from 2D monolayers to 3D spheroids.
- Previous proteome analyses identified over 5000 proteins with altered accumulation in spheroid cells.
Purpose of the Study:
- To investigate post-translational modifications (PTMs) in proteins that accumulate in cancer spheroids under simulated microgravity.
- To identify specific PTMs and their locations on proteins involved in spheroid formation.
Main Methods:
- Proteome analysis of FTC-133 thyroid and MCF-7 breast cancer cells in 1g monolayers and 3D spheroids (3 and 14 days simulated microgravity).
- Literature-based search for experimentally determined PTMs on selected proteins using SPARQL queries and the dbPTM database.
Main Results:
- Identified 72 classes of PTMs, including phosphorylation, glycosylation, ubiquitination, and acetylation.
- Found that 35 out of 69 investigated proteins exhibit modifications at N6 lysine residues.
Conclusions:
- PTMs play a significant role in the altered growth behavior of cancer cells forming spheroids in microgravity.
- Specific PTMs, particularly lysine modifications, are critical for spheroid formation and may represent novel therapeutic targets.
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