CD147 at the crossroads of glycoprotein networks, metabolic reprogramming, and metastatic progression.

CD147 (also known as EMMPRIN or Basigin), a transmembrane glycoprotein of the immunoglobulin superfamily, functions as a pivotal regulator of tumor progression. It coordinates key oncogenic processes-including metabolic adaptation, chemoresistance, angiogenesis, and immune modulation-through an extensive network of protein-protein interactions. Metabolic reprogramming not only reshapes the intrinsic metabolic circuitry of tumor cells but also promotes the establishment of a pre-metastatic niche that facilitates metastatic seeding and outgrowth via dynamic metabolic crosstalk with immune and stromal components. Here, we review current evidence showing that CD147 mediates PMN formation by promoting immune evasion, metabolic adaptation, and stromal remodeling. Through the coordination with membrane-associated glycoproteins-including CD44, epidermal growth factor receptor (EGFR), integrins, CD280 (uPARAP/Endo180/MRC2), and CD276, CD147 orchestrates intracellular signaling events that drive cancer cell metabolic adaptation. These interactions contribute to metabolic reprogramming across glucose, lipid, amino acid, and mitochondrial pathways, thereby linking CD147-mediated metabolic plasticity to tumor dissemination and metastasis. By integrating insights into immune and stromal modulation within the tumor microenvironment (TME), this review highlights the multifaceted roles of CD147 and its glycoprotein interactome in shaping the metastatic niche.