Ricerc@Sapienza

The tumor microenvironment (TME) is a critical regulator of cancer progression in metastatic malignancies and its biochemical composition is of prime importance for the regulation of metastases metabolism, proliferation, and motility. In fact, Metastases account for the great majority of cancer-associated deaths, in particular, Non-Small Cell Lung Cancer (NSCLC) metastases. NSCLC has some preferential sites for TME, the future metastases site, in particular the brain. In fact, Recent evidence have shown that the TME is characterized by its nutrient availability and heterogeneity in particular amino acids (1,2). Studies on such AA have gained more attention because of their key role in reprogramming metastatic cell metabolism in order to produce building blocks needed for sustaining cell survival in a foreign TME. Thereby, the high proliferative capacity of cancer cells and the increased metabolic demand/output, render up these cells dependent on continuous exogenous uptake of certain AA when intracellular synthesis is not adequate to deal with the metabolic requirements.
In fact, despite their ability to synthesize nonessential amino acids, NSCLC is unable to maintain sufficient amino acids pools by de novo synthesis under nonessential amino acids deprivation conditions in particular serine and glycine (3). Therefore, NSCLC show metabolic reliance on the exterior supply of these amino acids. At this point, the influence of the cellular metabolism on the selectivity of the favorable TME is still unclear. For these aims, we would evaluate the role of these peculiar amino acids in the motility capability and the metabolic reshaping of NSCLC during metastatization. This would clarify the development of NSCLC metastases in specific sites rather than in others.
1- Zhengtao X. et al. 2019. NATURE COMMUNICATIONS | 10:3763 |
2- Quail, D. F. & Joyce, J. A.2017. Cancer Cell 31, 326-341.
3- Sarah E., et al. 2020. Cell Metabolism 31, 339-350