AMPK Signaling in Cancer Metabolism

Adenosine monophosphate–activated protein kinase (AMPK) is a central metabolic sensor that maintains cellular energy homeostasis by coordinating catabolic and anabolic pathways. In cancer cells, dysregulated AMPK signalling underpins the metabolic reprogramming that supports rapid proliferation, survival under nutrient stress and adaptation to hypoxia. Activation of AMPK inhibits the mammalian target of rapamycin complex 1 (mTORC1), suppresses de novo lipid and protein synthesis and promotes autophagy. Conversely, under certain contexts, AMPK can act as a pro-survival signal, enabling tumour cells to withstand cytotoxic therapies by shifting metabolism towards oxidative phosphorylation and enhancing mitochondrial biogenesis. The dual roles of AMPK in tumour suppression and stress adaptation reflect a complex network of upstream kinases, upstream energy sensors and downstream effectors, with important implications for therapeutic targeting. Understanding the interplay between AMPK, metabolic substrates and the tumour microenvironment is crucial for exploiting metabolic vulnerabilities and improving outcomes in diverse malignancies.

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AMPK Signaling in Cancer Metabolism publication trend

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Technical terms

AMPK (Adenosine monophosphate–activated protein kinase): A serine/threonine kinase that senses changes in cellular AMP : ATP ratio and regulates energy balance by modulating metabolic pathways.

mTORC1 (Mammalian target of rapamycin complex 1): A multi-protein complex that promotes anabolic processes such as protein and lipid synthesis, inhibited by AMPK under low-energy conditions.

EMT (Epithelial–mesenchymal transition): A biological process by which epithelial cells adopt mesenchymal traits, increasing motility and invasiveness, often regulated by metabolic signals.

Tumour microenvironment: The local cellular milieu surrounding a tumour, including immune cells, fibroblasts, vasculature and extracellular matrix, which influences cancer metabolism and progression.

Metabolic reprogramming: The alteration of cellular metabolic pathways in cancer cells to support rapid growth, survival under stress and adaptation to environmental changes.

References

1. Impact of AMPK on cervical carcinoma progression and metastasis. Cell Death & Disease (2023).
2. AMPK–a key factor in crosstalk between tumor cell energy metabolism and immune microenvironment?. Cell Death Discovery (2024).
3. AMPK Activation Serves as a Common Pro-Survival Pathway in Esophageal Adenocarcinoma Cells. Biomolecules (2024).