Caveolin-1 mediates cellular distribution of HER2 and affects trastuzumab binding and therapeutic efficacy

• DOI: 10.1038/s41467-018-07608-w
• Publication Date: 2018-11-27T15:47:47Z
• Authors: Patrícia M. R. Pe...; Sai Kiran Sharma; Lukas M. Carter; Kimberly J. Edwards; Jacob Pourat; Ashwin Ragupathi; Yelena Y. Janjigian; Jeremy C. Durack; Jason S. Lewis
• Keywords: Caveolin 1; Cell membrane

Abstract Human epidermal growth factor receptor 2 (HER2) gene amplification and/or protein overexpression in tumors is a prerequisite for initiation of trastuzumab therapy. Although HER2 cell membrane receptor, differential rates endocytosis and recycling engender dynamic surface pool HER2. Since must bind to the extracellular domain HER2, depressed hinders binding. Using vivo biological models cultures fresh human tumors, we find that caveolin-1 (CAV1) involved dynamics within context endocytosis. The translational significance this finding highlighted by our observation temporal CAV1 depletion with lovastatin increases half-life availability at resulting improved binding therapy against HER2-positive tumors. These data show important role plays effectiveness target