GEO series
Effect of lactate accumulation on translation and transcription in MDA-MB-231 breast cancer cells
GSE297242
Homo sapiens
Expression profiling by high throughput sequencing; Other
12 samples
Submitted 2026/08/01
Platform GPL34284
Summary
Dynamic coordination of energy metabolism and protein synthesis is pivotal to cell fitness, especially in cancer cells that frequently encounter microenvironmental challenges. Yet it remains unclear whether this rapid communication depends on complex regulatory signaling pathways or can be governed by a single molecule. Here, we show that intracellular accumulation of lactate, a central product of glycolysis, is sufficient to acutely repress mRNA translation. Mechanistically, lactate is charged to the 3′ end of tRNA, a site canonically reserved for amino acids, generating translation-defective lactyl-tRNAs. This mechanism may have evolved to restrict protein synthesis during metabolic imbalance, such as when glycolytic activity exceeds lactate clearance, and is particularly relevant in highly glycolytic cancer cells, which frequently experience prolonged hypoxia and elevated lactate levels. Notably, triple-negative breast cancer (TNBC) cells evade this repression by maintaining low intracellular lactate, even under hypoxic stress. Blocking lactate export via monocarboxylate transporter (MCT) inhibition re-establishes translational repression, diminishes cancer cell fitness under metabolic stress, and impairs tumor progression. These findings uncover a unique metabolite-tRNA charging event that directly rewires translational output and reveal a metabolic vulnerability with therapeutic potential.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE297242_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 12 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1263382 and SRA study SRP586076. Searching any of these in the dataset finder brings you back here.
Study design
3 × total RNA, MDA-MB-231 cells, DMSO, vs 3 × total RNA, MDA-MB-231 cells, AZD0095, vs 3 × Ribosome protected fragments, MDA-MB-231 cells, DMSO, vs 3 × Ribosome protected fragments, MDA-MB-231 cells, AZD0095,
Supports a between-group comparison across 12 samples.
4 replicated groups read from 12 sample titles; they account for 12 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8986684 total RNA, MDA-MB-231 cells, DMSO, replicate 1
- GSM8986685 total RNA, MDA-MB-231 cells, DMSO, replicate 2
- GSM8986686 total RNA, MDA-MB-231 cells, DMSO, replicate 3
- GSM8986687 total RNA, MDA-MB-231 cells, AZD0095, replicate 1
- GSM8986688 total RNA, MDA-MB-231 cells, AZD0095, replicate 2
- GSM8986689 total RNA, MDA-MB-231 cells, AZD0095, replicate 3
- GSM8986690 Ribosome protected fragments, MDA-MB-231 cells, DMSO, replicate 1
- GSM8986691 Ribosome protected fragments, MDA-MB-231 cells, DMSO, replicate 2
- GSM8986692 Ribosome protected fragments, MDA-MB-231 cells, DMSO, replicate 3
- GSM8986693 Ribosome protected fragments, MDA-MB-231 cells, AZD0095, replicate 1
- GSM8986694 Ribosome protected fragments, MDA-MB-231 cells, AZD0095, replicate 2
- GSM8986695 Ribosome protected fragments, MDA-MB-231 cells, AZD0095, replicate 3
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