ASPA loss reprograms cancer-associated fibroblasts metabolism to potentiate tumor progression
| Autor: | Capó-Serra, Catalina, Viera, Cristina, Astobiza, Ianire, Calvo, Fernando, Carracedo, Arkaitz |
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| Rok vydání: | 2022 |
| Popis: | Trabajo presentado en el European Association for Cancer Research (EACR) Congress, celebrado en Sevilla (España) del 20 al 23 de junio de 2022. Cancer Associated Fibroblasts (CAFs) are the major population of the tumor microenvironment, and they present a pathologically activated phenotype that promotes extracellular matrix (ECM) remodeling activity and pro-tumorigenic signaling to cancer cells. CAFs may also present metabolic adaptations such as enhanced anaerobic glycolysis that generate metabolites to fuel cancer cell growth. However, how metabolic reprogramming assists in the activation of fibroblasts, and influence their pro-tumor behavior is not well defined. Here we unravel Aspartoacylase enzyme (ASPA), which is consistently downregulated in CAFs of several tumor types, as a potential regulator of CAF aggressive phenotype. Accordingly, the modulation of ASPA expression in CAFs affect their levels of CAF marker expression, extracellular matrix remodeling capacity and the crosstalk to cancer cells. Understanding the role and mechanisms of action of ASPA in CAFs may illuminate the intricate metabolic crosstalk between tumor and stroma, and how metabolic adaptations affect signaling and epigenetic reprogramming to enable the emergence of a fully pro-tumor CAF phenotype.We expect these advances to inform strategies to restrain tumor-promoting behaviors in CAFs and compromise tumor progression. |
| Databáze: | OpenAIRE |
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