Dietary palmitic acid establishes an epigenetic memory that promotes metastasis - implications of neural-related processes in enhancing dissemination
- Autores: Diana Domínguez Rodríguez
- Directores de la Tesis: Salvador Aznar Benitah (dir. tes.)
- Lectura: En la Universitat Pompeu Fabra ( España ) en 2021
- Idioma: español
- Materias:
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- Resumen
Metastatic disease still accounts for 90% of cancer-related deaths, highlighting the lack of knowledge about its molecular mechanisms. Previous work from our laboratory has demonstrated the importance of lipid metabolism in metastatic disease, highlighting the role of the fatty acid (FA) receptor CD36 as a marker of metastasis-initiating cells in several cancer types. Here, I describe the work we have done on exploring the implications of distinct dietary FAs in modulating metastatic dissemination through the CD36 molecule.
Our data points towards the ability of palmitic acid (PA) to enhance distant dissemination while exerting a long-lasting impact on both the epigenome and transcriptome of tumor cells. This “epigenetic memory” is exemplified by stable changes in the H3K4me3 profile of cancer cells, which are partly dependent on the Set1A/COMPASS histone methyltransferase activity.
The PA-triggered pro-metastatic memory predominantly targets neural-related genes, resulting in the stimulation of neural processes such as intra-tumor Schwann cell generation and perineural invasion, traits that correlate with aggressive forms of different tumors. Based on in silico approaches using tumor transcriptomic data, we identified the neural-related transcription factor EGR2 and the neuropeptide galanin (GAL) as downstream effectors of the PA/CD36 axis in metastasis induction. Therefore, we propose that dietary, neural-related, and epigenetic interventions are potential therapeutic strategies to hamper malignant dissemination.
