Séminaire externe : Erika Cosset
de 11:00 à 12:00
|S'adresser à||Julie Carnesecchi|
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Séminaire externe : Erika Cosset (Centre de Recherche Contre le Cancer, Lyon, France)
"Galectin-3/Macropinocytosis addiction: an Achilles’ heel that could be exploited for a subset of glioblastoma patients"
Tumors must survive microenvironmental stresses, such as nutriment deprivation, low levels of oxygen and anticancer treatments. To do so, tumor cells have developed numerous adaptation mechanisms, and we have recently shown that induction of macropinocytosis is associated with tumor cell survival. In our previous work, we determined that Galectin-3 (Gal-3)/KRAS/αvβ3 integrin complex acts as a driver of macropinocytosis, an endocytic process by which tumor cells are able to engulf large amounts of nutrients from the local microenvironment. In glioblastoma (GBM) cells, which do not harbor mutations in KRAS, we interestingly uncovered the same phenomenon of macropinocytosis induction, which was associated with the mesenchymal subset of GBM. Indeed, by using patient-derived GSCs, we identified and characterized a subset of Gal-3high GBM tumors within the mesenchymal subtype that are addicted to Gal-3-mediated. Moreover, by defining a Gal-3/macropinocytosis molecular signature based on a list of Gal-3/survival-associated genes, we were able to predict sensitivity to this dependency pathway and provide proof-of-principle for new therapeutic strategies to exploit Gal-3 and its partners for a subset of GBM patients. Therefore, our findings provide a strong rationale for investigating macropinocytosis as a druggable vulnerability in several cancer types identified to be macropinocytosis-addicted and not only in cancer associated with oncogenic KRAS, as previously reported.
Hôte : Julie Carnesecchi
Lundi 14 novembre
Salle des thèses