Cancer cells forgo translating mRNA transcribed from genes of nonspecialized tasks

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. © 2024 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.