L'asse SMAD1-MCAM endoteliale facilita la resistenza al sunitinib e la progressione del carcinoma renale a cellule chiare via segnalazione LAMB1-ITGB1.

Clear cell renal cell carcinoma (ccRCC) is characterized by high metastatic potential and frequent resistance to conventional therapies, highlighting the need for a deeper understanding of its tumor microenvironment. Here, we integrated single-cell RNA sequencing and spatial transcriptomics from large ccRCC cohorts to map the cellular landscape of ccRCC. We identified a distinct stromal cell subpopulation, Melanoma Cell Adhesion Molecule, MCAM+ endothelial cells (MCAM+ ECs), which spatially associates with EMT-like tumor cells and promotes disease progression. Mechanistically, our findings suggest that MCAM+ ECs facilitate metastatic features via a LAMB1-ITGB1-RhoA signaling axis, contributi