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β-catenin oncogenic activation rewires fatty acid catabolism to fuel hepatocellular carcinoma
  1. Alexandra Montagner1,
  2. Laurent Le Cam2,3,
  3. Hervé Guillou4
  1. 1 Institut National de la Santé et de la Recherche Médicale (INSERM), U1048 and Université Toulouse III, I2MC, Toulouse, Midi-Pyrénées, France
  2. 2 IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier, Languedoc-Roussillon, France
  3. 3 Equipe Labellisée Ligue Contre le Cancer, Montpellier, France
  4. 4 Toxalim, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France
  1. Correspondence to Dr Hervé Guillou, Integrative Toxicology and Metabolism, INRA ToxAlim, Toulouse 31027, France; herve.guillou{at}

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Liver cancer is a major public health issue and generally considered an inflammation-related cancer developing in response to genotoxic exposure or in patients with viral, alcoholic or non-alcoholic hepatitis. It is a leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) representing 90% of primary liver cancer cases. Various pathways are dysregulated in HCC, including p53 and other cell cycle regulators, chromatin modifiers, oxidative stress, insulin and growth factor signalling, and Wnt/β-catenin signalling. In this issue, Senni and colleagues1 demonstrate the role of fatty acid oxidation as a source of energy in the metabolic adaptation triggered by β-catenin oncogenic activation in hepatocytes. This work describes an atypical cancer cell addiction to fatty acids and represents an important discovery that may pave the way for novel therapeutics.

The Wnt/β-catenin pathway2 plays a key role in many aspects of hepatic homeostasis, including the regulation of unique liver features, such as metabolic zonation.3 In the absence of Wnt stimulation, the cytosolic concentration of β-catenin remains low because a multiprotein complex that includes the tumour suppressor adenomatous polyposis coli (APC) promotes the phosphorylation of β-catenin, and thereby its proteasomal degradation. In response to Wnt stimulation, the degradation complex is recruited to the plasma membrane, which leads to β-catenin stabilisation, …

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  • Contributors All authors contributed to writing and revising the commentary.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

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