Caveolin-1-mediated albumin uptake pathway (CAV1-mediated albumin uptake)

The Caveolin-1-mediated albumin uptake pathway is a specialized endocytic and transcytotic mechanism primarily utilized by endothelial and certain cancer cells to internalize and transport albumin [2, 6]. This pathway is initiated by the binding of albumin to the 60 kDa glycoprotein receptor (gp60 or albondin), which subsequently recruits and activates caveolin-1, the principal structural protein of caveolae [3, 7]. Activation of this axis triggers Src kinase-mediated phosphorylation and G-protein signaling, leading to the invagination of the plasma membrane and the formation of caveolae vesicles that transport albumin across the vascular endothelium or into the cytoplasm [7, 8]. In oncology, this pathway is exploited for the delivery of albumin-bound therapeutics, such as nab-paclitaxel (Abraxane), which leverage the high demand for albumin in rapidly proliferating tumor cells [2, 11]. Consequently, the expression levels of caveolin-1 and gp60 serve as critical determinants of drug efficacy and potential biomarkers for patient selection [2, 6]. Beyond drug delivery, the pathway plays significant roles in lipid homeostasis, glucose metabolism, and the pathogenesis of diseases like atherosclerosis and diabetic nephropathy [1, 9, 12].

Other names

Caveolae-mediated albumin uptakegp60-mediated albumin transcytosisAlbondin-mediated pathwayAlbumin-gp60-Caveolin-1 axisAlbumin receptor pathway

Albumin binds to the gp60 (albondin) receptor on the cell surface, which then associates with caveolin-1 to trigger caveolae formation and subsequent transcytosis or endocytosis of the albumin-drug complex [3, 7, 8].