Kinase Signaling Pathways in Cancer Metabolism

Cancer cells rewire their metabolic circuits to support rapid proliferation, survival under stress and metastatic spread. Central to this rewiring are kinase signalling pathways that sense nutrient and energy status, transmit growth cues and adjust anabolic and catabolic processes. Oncogenic kinases such as PI3K and AKT activate downstream effectors including mTOR to stimulate glycolysis, lipid synthesis and protein translation, while suppressing autophagy. Conversely, the LKB1–AMPK axis operates as an energy sensor, arresting growth when ATP levels fall and promoting oxidative metabolism and autophagy. Emerging evidence highlights that AMPK-related kinases such as NUAK1 and NUAK2 fine-tune these responses, influencing mitochondrial function, glycolytic flux and redox balance. Crosstalk between stress-activated kinases (for example, JNK) and metabolic regulators integrates environmental signals such as hypoxia or nutrient deprivation, thereby modulating tumour cell adaptation. Dysregulation of these kinase networks not only fuels biomass accumulation and ATP production but also confers resistance to chemotherapy and promotes invasion. Targeting key nodes in kinase-driven metabolic reprogramming offers a promising avenue for selectively impairing tumour energetics and sensitising cancer cells to existing therapies.

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Kinase Signaling Pathways in Cancer Metabolism publication trend

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Technical terms

Kinase: Enzyme that transfers a phosphate group from ATP to specific substrates, regulating signal transduction and metabolic pathways.

Phosphorylation: Post-translational modification in which a phosphate group is covalently attached to a protein, altering its activity, localisation or stability.

Glycolysis: Metabolic pathway that converts glucose to pyruvate, generating ATP and metabolic intermediates for biosynthesis.

Mitochondrial respiration: Process by which cells use oxygen to produce ATP via the electron transport chain and oxidative phosphorylation.

PI3K/AKT pathway: Signalling cascade initiated by phosphoinositide 3-kinase, leading to activation of AKT kinase and downstream promotion of growth, survival and metabolism.

Metabolic reprogramming: Adaptation of cellular metabolic pathways to meet altered energy and biosynthetic demands, often observed in cancer.

References

1. Cytosolic NUAK1 Enhances ATP Production by Maintaining Proper Glycolysis and Mitochondrial Function in Cancer Cells. Frontiers in Oncology (2020).
2. NUAK1 promotes tumor metastasis through upregulating slug transcription in esophageal squamous cell carcinoma. Cancer Cell International (2023).
3. Discovery of a novel NUAK1 inhibitor against pancreatic cancer. Biomedicine & Pharmacotherapy (2022).