Metabolic flexibility in cell systems

Mammalian cells rely on two major pathways to generate energy and build essential biomolecules: glycolysis, which occurs in the cytoplasm, and mitochondrial oxidative metabolism. These pathways not only fuel cellular energy demands but also provide critical intermediates for growth.

Hanne R. Hagland’s research explores how these metabolic routes drive cancer progression and how metabolites themselves influence gene regulation.

Cancer Metabolism

Tumors are highly heterogeneous in their genetic and protein profiles. Yet, one common feature of rapidly growing cells is their dependence on nutrients, particularly glucose and glutamine, to supply building blocks for proliferation.

Hagland’s work has shown that while some cancer cells can adapt and utilize diverse substrates, others are strictly dependent on glucose for survival. This metabolic preference is linked to mutations in key growth pathways and is reflected in the cells’ metabolic signatures. Identifying which tumors are glycolytic and which are not may help tailor more effective treatment strategies.

Protein Regulation and Mitochondrial Function

Her research also investigates how cancer cells sustain high glycolytic flux and the role of mitochondria in these processes. Under cellular stress, mitochondrial function and fuel flexibility determines the cells' ability to survive stress. Identifying proteins and signalling pathways involved in these stress resistance together with mitochondridal functional tests is a research focus area of the group. One protein is of particular interest with the uncoupling proteins (UCPs), which can modulate mitochondrial function to maintain metabolic flexibility, independent of ATP production. Little is known about how UCPs are regulated in different cancer types, and Hagland’s team aims to uncover these mechanisms.

Clinical Collaboration

Hanne R. Hagland collaborates with the Gastrosurgical Research Group at Stavanger University Hospital (SUH), focusing on gastrointestinal cancers. Collaborative research projects include studying the metabolic flexibility of patient derived cancer organoids from surgically resected speciments of pancreatic cancer patients treated at SUH. These patients are included in the GITAN biobank after written concent.

The goal is to bridge the knowledge gap from lab to clinic by designing clinically relevant research projects that can improve disease management. A key area of interest is how mitochondrial fitness and flexibility differs between normal and cancerous tissue—and how these changes may be linked to shifts in metabolic pathways.

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