Fibroblast activation protein drives tumor metastasis via a protease-independent role in invadopodia stabilization

• DOI: 10.1016/j.celrep.2023.113302
• Publication Date: 2023-10-19T16:15:27Z
• Authors: Maurish Bukhari; Navneeta Patel; Rosa Fontana; Miguel Santiago-M...; Yike Jiang; Dongmei Li; Kersi Pestonjamasp; Victoria J. Chris...; Kenneth W. Jackson; Patrick A. McKee; Jing Yang
• Keywords: Invadopodia

During metastasis, tumor cells invade through the basement membrane and intravasate into blood vessels then extravasate distant organs to establish metastases. Here, we report a critical role of transmembrane serine protease fibroblast activation protein (FAP) in metastasis. Expression FAP TWIST1, metastasis driver, is significantly correlated several types human carcinomas, required for TWIST1-induced breast cancer lung. Mechanistically, localized at invadopodia invadopodia-mediated extracellular matrix degradation independent its proteolytic activity. Live cell imaging shows that association precursors with promotes stabilization growth mature invadopodia. Together, our study identified as functional target TWIST1 driving via promoting uncovered activity-independent stabilizing maturation.