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Updated: Jul 1, 2025

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
Cancer cells forgo translating mRNA transcribed from genes of nonspecialized tasks
Mahmoud Ahmed1, Trang Minh Pham1, Hyun Joon Kim2
1Department of Biochemistry and Convergence Medical Sciences, Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, South Korea.
Abstract:
The coupling of transcription and translation enables prokaryotes to regulate mRNA stability and reduce nonfunctional transcripts. Eukaryotes evolved other means to perform these functions. Here, we quantify the disparity between gene expression and protein levels and attempt to explain its origins. We collected publicly available simultaneous measurements of gene expression, protein level, division rate, and growth inhibition of breast cancer cells under drug perturbation. We used the cell lines as entities with shared origin, different evolutionary trajectories, and cancer hallmarks to define tasks subject to specializing and trading-off. We observed varying average mRNA and protein correlation across cell lines, and it was consistently higher for the gene products in the cancer hallmarks. The enrichment of hallmark gene products signifies the resources invested in it as a task. Enrichment based on mRNA or protein abundance corresponds to the relative resources dedicated to transcription and translation. The differences in gene- and protein-based enrichment correlated with nominal division rates but not growth inhibition under drug perturbations. Comparing the range of enrichment scores of the hallmarks within each cell signifies the resources dedicated to each. Cells appear to have a wider range of enrichment in protein synthesis relative to gene transcription. The difference and range of enrichment of the hallmark genes and proteins correlated with cell division and inhibition in response to drug treatments. We posit that cancer cells may express the genes coding for seemingly nonspecialized tasks but do not translate them to the corresponding proteins. This trade-off may cost the cells under normal conditions but confer benefits during stress.
Insights
Cancer cells may prioritize gene expression over protein production for certain functions, a trade-off impacting cell division and drug response.
Area of Science:
- Molecular Biology
- Cancer Cell Biology
- Systems Biology
Background:
- Prokaryotes couple transcription and translation for mRNA regulation.
- Eukaryotes utilize distinct mechanisms for gene expression control.
- Understanding gene and protein level disparities is crucial in cancer research.
Purpose of the Study:
- To quantify the discrepancy between gene expression and protein levels in breast cancer cells.
- To investigate the origins of these disparities, particularly in relation to cancer hallmarks.
- To correlate these differences with cell division rates and drug responses.
Main Methods:
- Utilized publicly available data on gene expression, protein levels, division rate, and drug-induced growth inhibition.
- Analyzed breast cancer cell lines with shared origins but different evolutionary paths.
- Examined resource allocation to specific cellular tasks, including cancer hallmarks, at transcriptional and translational levels.
Main Results:
- Observed variable mRNA-protein correlation across cell lines, higher for cancer hallmark gene products.
- Found that differences in gene- and protein-based enrichment correlated with cell division rates but not drug-induced growth inhibition.
- Noted a wider range of protein synthesis enrichment compared to gene transcription enrichment within cells.
Conclusions:
- Cancer cells may strategically under-translate certain genes, potentially conserving resources or adapting to stress.
- This trade-off between gene expression and protein production influences cell division and response to drug treatments.
- The differential enrichment of hallmark genes and proteins offers insights into cancer cell adaptation and survival strategies.
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