Obesity and melanoma: a new link







extracellular vesicle

Laurence NiétoMELASPHINX Team – Métabolisme du céramide dans le mélanome : des mécanismes moléculaires à l’immunothérapie

Obesity is a recognized factor for increased risk and poor prognosis of many cancers, including melanoma. Here, using mouse models of melanoma, we show that obesity increases melanoma agressiveness by supporting tumor growth and metastasis thereby reducing survival. This effect is associated with a decrease in p16INK4A protein expression in tumors. Actually, fat cells (adipocytes) downregulate p16INK4A in melanoma cells as they transfer β-catenin from adipocytes to melanoma cells in small vesicles, the so-called extracellular vesicles, which represses p16INK4A, a major events of melanoma development. In obesity, adipocytes have a stronger effect than those from lean individuals, as they release more vesicles.

Impact clinique et perspectives

This work expands our understanding of the cooperation between adipocytes and tumors, particularly in obesity, and should encourage hospital practitioners to monitor more closely this risk of cancer in obese but also overweight subjects. Moreover, the prevalence of aberrations that impact the p16INK4A and related pathway, makes it an attractive therapeutic target to prevent metastatic melanoma, particularly in obese individuals.

Adipocytes secrete extracellular vesicles, which contain beta-catenin that is transferred to melanoma cells. Once transferred, beta catenin repressed p16INK4A expression and, consequently, increased melanoma aggressiveness. This process is amplified in obesity.

Discover the published article

J Invest Dermatol. 2022 Sep;142(9):2488-2498.e8.doi: 10.1016/j.jid.2022.01.026. Epub 2022 Feb 9.
Adipocyte Extracellular Vesicles Decrease p16 INK4A in Melanoma: An Additional Link between Obesity and Cancer
Ikrame Lazar, Emily Clement, Lorry Carrié, David Esteve, Stéphanie Dauvillier, Mohamed Moutahir, Stéphane Dalle, Véronique Delmas, Nathalie Andrieu-Abadie, Lionel Larue, Catherine Muller, Laurence Nieto

Collaborations and acknowledgements

  • Main collaborations: IPBS (Pr C. Muller Team) and Institut Curie (Dr L. Larue Team)
  • Fundings: fondation ARC, ligue contre le cancer and société française de dermatologie (SFD)
Centre de Recherches en Cancérologie de Toulouse

Toulouse Cancer Research Center (Oncopole)

Toulouse – FR

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