Fig. 5.

The cancer invasion and metastasis and its targeted therapy. The tumor metastasis process consists of multiple steps. Initially, tumor cells invade the surrounding stroma and extracellular matrix from the primary tumor site, and then intravasate into the bloodstream or the lymphatics. Subsequently, tumor cells arrest in the circulation and arrive at distant organ sites, followed by extravasating and invading the parenchyma of distant tissues. Finally, tumor cells adapt to the new microenvironment and grow to form metastatic colonization. EMT is the basic embryonic developmental process that transforms polarized non-motile epithelial cells into motile and invasive mesenchymal cells. Multiple cellular stress conditions including hypoxia, inflammation, metabolic stress, and signaling cascades, can induce the expression of EMT transcription factors and prompt tumor metastasis. Meanwhile, MET amplification and mutation, the transcriptional dysregulation of c-MET, degradation deficiency, and abnormal HGF production result in the abnormal expression of HGF/c-MET and tumor progression. Various inhibitors including MMP inhibitors and HGF/c-MET inhibitors have been developed and emerging as promising tools in the suppression of tumor metastasis. c-MET mesenchymal-epithelial transition factor, EMT epithelial-mesenchymal transition, HGF hepatocyte growth factor, MMPs matrix metalloproteinases