Metabolic Reprogramming in Breast Cancer

Metabolic reprogramming is a defining hallmark of breast cancer, encompassing diverse alterations in energy utilisation, biosynthetic pathways and intracellular signalling. Tumour cells frequently adopt aerobic glycolysis—also known as the Warburg effect—to generate ATP rapidly and supply intermediates for nucleotide, amino acid and lipid synthesis. Concurrently, many breast cancers enhance glutaminolysis to feed the tricarboxylic acid cycle and maintain redox balance, while driving de novo lipogenesis to support membrane biogenesis and signalling. These shifts are orchestrated by oncogenic drivers such as MYC amplification, PIK3CA mutations and dysregulated PI3K–AKT–mTOR signalling, as well as by tumour-suppressor loss (for example TP53). Distinct molecular subtypes display characteristic metabolic phenotypes: oestrogen receptor-positive tumours often rely on oxidative phosphorylation, whereas triple-negative breast cancers exhibit pronounced glycolytic and lipid dependencies. Metabolic plasticity enables adaptation to hypoxia, nutrient scarcity and therapeutic stress, contributing to chemoresistance and metastatic competence. A deeper understanding of these interconnected metabolic circuits is vital for the development of precision therapies that exploit specific vulnerabilities in breast cancer energy and biosynthetic programmes.

Research from Nature Portfolio

Curcumin has been shown to attenuate the Warburg effect by down-regulating pyruvate kinase M2 (PKM2) via inhibition of the mTOR–HIF-1α axis. This study demonstrated that curcumin treatment reduces glucose uptake and lactate production in breast cancer cell lines, and that these effects are reversed by enforced PKM2 expression. Mechanistically, mTOR inhibition leads to diminished HIF-1α activity, thereby suppressing PKM2 transcription and glycolytic flux. The findings reveal a novel metabolic mechanism for curcumin’s anticancer activity and identify PKM2 as a key node for therapeutic intervention in glycolysis-addicted tumours.

Metabolic Reprogramming in Breast Cancer publication trend

The graph below shows the total number of articles in metabolic reprogramming in breast cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Aerobic glycolysis (Warburg effect): conversion of glucose to lactate in the presence of oxygen, supporting rapid ATP production and biosynthesis.

Oxidative phosphorylation (OXPHOS): mitochondrial process by which electrons flow through the respiratory chain to generate ATP via chemiosmotic coupling.

mTOR: mechanistic target of rapamycin, a serine/threonine kinase integrating nutrient and growth signals to regulate protein synthesis and metabolism.

Glutaminolysis: catabolism of glutamine to produce tricarboxylic acid cycle intermediates and support redox homeostasis.

SREBP1: sterol regulatory element-binding protein 1, a transcription factor that controls genes involved in fatty acid and lipid biosynthesis.

Supercomplex: assembly of multiple mitochondrial respiratory chain complexes that enhances electron transport efficiency.

References

1. RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer. Military Medical Research (2023).
2. Noncanonical role of singleminded-2s in mitochondrial respiratory chain formation in breast cancer. Experimental & Molecular Medicine (2023).
3. Metabolism-regulating non-coding RNAs in breast cancer: roles, mechanisms and clinical applications. Journal of Biomedical Science (2024).
4. Metabolic Reprogramming in Breast Cancer and Its Therapeutic Implications. Cells (2019).
5. Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition. Scientific Reports (2018).