HIF2α, Hepcidin and their crosstalk as tumour-promoting signalling.

Vincenzo Formica, Silvia Riondino, Cristina Morelli, Simona Guerriero, Federica D'Amore, Antonio Di Grazia, Giovanna Del Vecchio Blanco, Giuseppe Sica, Hendrik-Tobias Arkenau, Giovanni Monteleone, Mario Roselli

Journal: British journal of cancer 2023;129(2):222-236

PMID: 37081189

Abstract

Not all aspects of the disruption of iron homeostasis in cancer have been fully elucidated. Iron accumulation in cancer cells is frequent for many solid tumours, and this is often accompanied by the contemporary rise of two key iron regulators, HIF2α and Hepcidin. This scenario is different from what happens under physiological conditions, where Hepcidin parallels systemic iron concentrations while HIF2α levels are inversely associated to Hepcidin. The present review highlights the increasing body of evidence for the pro-tumoral effect of HIF2α and Hepcidin, discusses the possible imbalance in HIF2α, Hepcidin and iron homeostasis during cancer, and explores therapeutic options relying on these pathways as anticancer strategies.

© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

Address: Medical Oncology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Viale Oxford, 81, 00133, Rome, Italy. [email protected].; Medical Oncology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Viale Oxford, 81, 00133, Rome, Italy.; PhD Program in Systems and Experimental Medicine (XXXV cycle), University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.; Gastroenterology Unit, Department of Systems Medicine, University of Rome Tor Vergata, 00133, Rome, Italy.; Department of Surgery, University of Rome Tor Vergata, Rome, Italy.; Drug Development Unit, Sarah Cannon Research Institute UK, London, UK.
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