HGF/SF-Met Signaling Regulates Tumor Cell Plasticity, Morphology and Motility Dynamics

Yossi Levi Sari Natan Ohad Doron Judith Horev Dganit Shkedy Ilan Tsarfaty
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel-Aviv University

Complications from metastasis rather than the primary tumor are the cause of death in the majority of cancer patients. Hepatocyte growth factor/scatter factor-Met tyrosine kinase receptor induce unique signaling and metabolic pathways leading to cell motility and metastasis. A novel analytical framework is introduced to detect and quantify alteration of morphological and kinetical features in single and group cell motility. The analysis combines and associates vast amount of spatiotemporal data across multiple experiments into quantitative measures. Using these novel analytical tools and physical modeling we demonstrate new modes of cell motility during single/collective migration of tumor cells induced by Met signaling. We also discovered the emergence of a waves of coordinated migration. These findings offer new insight and suggest a basic cellular and molecular mechanism controlling collective and single cell migration leading to metastasis. Inhibition of these signaling pathways reduces cell motility and metastasis.









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