In order to investigate the role of cell adhesion, mediated by cell-cell and cell-ECM interactions in the tumor microenvironment, in the molecular mechanism underlying ASS1 function, we compared the proteomes of HCC cells cultured as monolayers (2D) or spheroids (3D) to identify a global protein response in the different in vitro conditions (Fig. 1a). Here, ASS1 is linked to hepatocellular carcinoma.