Research Projects

Invadopodia, an actin-rich membrane protrusion formed by invasive cancer cells, is responsible for remodeling the extracellular matrix (ECM) for cancer invasion and metastasis. Various RTKs, such as EGFR and Met, regulate this process through their kinase activity. The Met oncoprotein, a member of the RTK family, promotes cell migration and cancer cell invasion. However, the mechanism behind invadopodia-induced cancer invasion remains unknown. This study aims to investigate the Met-driven invadopodia formation and invasion in breast cancer cell lines. MDA-MB-231 or MCF10A DCIS cells stimulated with HGF showed enhanced invadopodia-associated activity during ECM invasion. The study hypothesizes that Met is physically present at the invadopodia and has functional interaction with its key components. The HGF/Met axis triggers the surface delivery of invadopodia-associated metalloprotease MT1-MMP through physical association with the protease. In silico analysis indicates that MT1-MMP and Met can interact, and the interaction will be validated using GFP nanobody pulldown assay and FRET under in cellulo conditions. Further molecular docking analysis will be conducted to identify the motif of MT1-MMP that facilitates the interaction with Met. The study aims to provide a novel target for cancer therapy in TNBCs.