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• W2073621719 startingPage "1788" @default.
• W2073621719 abstract "Met tyrosine kinase has been implicated in tumorigenesis and metastasis; its overexpression and deregulation is often observed in cancer. Although Met's functions in cell motility has been studied extensively, its involvement in bleb-based, amoeboid motility is yet to be determined. The aim of this work is to study the role of Met in amoeboid cell motility and invasion. We show that aggressive breast cancer cells expressing high levels of endogenous Met, as well as HEK293T cells over expressing fluorescent Met, exhibit constitutive, ligand-independent Met activation, leading to Met-dependent membrane blebbing and amoeboid cell motility; HEK293T cells over expressing fluorescent Met were able to invade in three-dimensional matrix. Hyper-activated Met mutant significantly enhances blebbing and cell motility. Met inhibition by either a Met-specific inhibitor or by exogenous expression of a dominant-negative Met remarkably repressed membrane blebbing and invasion. Inhibition of Rho signaling pathway by a ROCK inhibitor also represses Met-induced blebbing, suggesting that Met regulates the blebbing machinery through Rho-ROCK pathway, which controls the actin-myosin contractile force. Either de-polymerization or hyper-polymerization of the actin cytoskeleton abrogates Met-induced blebbing, signifying that actin polymerization has a role in halting and retracting Met-induced mature blebs. Indeed, when blebs retract, membrane wrinkles containing high levels of Met and actin are generated, indicating localized formation of Met-signaling microdomains. We suggest that this bleb-based activity is induced by amplification of Met signaling in unique membrane domains generated by bleb retraction. Our results indicate that Met-induced blebbing has an important role in cell detachment, amoeboid motility and invasion ability, which are utilized by cancer cells for migration and metastasis." @default.
• W2073621719 created "2016-06-24" @default.
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• W2073621719 date "2013-05-13" @default.
• W2073621719 modified "2023-10-16" @default.
• W2073621719 title "Met-induced membrane blebbing leads to amoeboid cell motility and invasion" @default.
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• W2073621719 doi "https://doi.org/10.1038/onc.2013.138" @default.
• W2073621719 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23665680" @default.
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