Autophagy is associated with a robust specific transcriptional signature in breast cancer subtypes.

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Date publication

décembre 2020

Journal

Genes & cancer

Auteurs

Membres identifiés du Cancéropôle Est :
Mr MONNIEN Franck, Dr HERVOUET Eric, Dr PEIXOTO Paul, Dr DESPOUY Gilles, Pr FEUGEAS Jean-Paul


Tous les auteurs :
Grandvallet C, Feugeas JP, Monnien F, Despouy G, Valérie P, Michaël G, Hervouet E, Peixoto P

Résumé

Previous works have described that autophagy could be associated to both pro- and anti-cancer properties according to numerous factors, such as the gene considered, the step of autophagy involved or the cancer model used. These data might be explained by the fact that some autophagy-related genes may be involved in other cellular processes and therefore differently regulated according to the type or the grade of the tumor. Indeed, using different approaches of transcriptome analysis in breast cancers, and further confirmation using digital PCR, we identified a specific signature of autophagy gene expression associated to Luminal A or Triple Negative Breast Cancers (TNBC). Moreover, we confirmed that ATG5, an autophagy gene specifically expressed in TNBC, favored cell migration, whereas , an autophagy gene specifically associated with ER-positive breast cancers, induced opposite effects. We also showed that overall inhibition of autophagy promoted cell migration suggesting that the role of individual ATG genes in cancer phenotypes was not strictly dependent of their function during autophagy. Finally, our work led to the identification of as a potential biomarker associated to autophagy induction in breast cancers. This gene could become an essential tool to quantify autophagy levels in fixed biopsies, sort tumors according to their autophagy levels and determine the best therapeutic treatment.

Mots clés

autophagy, breast cancer, gene expression signature, transcriptome

Référence

Genes Cancer. 2020 Dec 31;11(3-4):154-168