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001-es BibID:	BIBFORM044944
Első szerző:	Wiedmann, Romina M.
Cím:	The V-ATPase-inhibitor archazolid abrogates tumor metastasis via inhibition of endocytic activation of the Rho-GTPase Rac1 / Romina M. Wiedmann, Karin von Schwarzenberg, Andrea Palamidessi, Laura Schreiner, Rebekka Kubisch, Johanna Liebl, Christina Schempp, Dirk Trauner, Gyorgy Vereb, Stefan Zahler, Ernst Wagner, Rolf Müller, Giorgio Scita, Angelika M. Vollmar
Dátum:	2012
Megjegyzések:	The abundance of the multimeric vacuolar ATP-dependent proton pump, V-ATPase, on the plasma membrane of tumor cells correlates with the invasiveness of the tumor cell, suggesting the involvement of V-ATPase in tumor metastasis. V-ATPase is hypothesized to create a proton efflux leading to an acidic pericellular microenvironment that promotes the activity of proinvasive proteases. An alternative, not yet explored possibility is that V-ATPase regulates the signaling machinery responsible for tumor cell migration. Here, we show that pharmacologic or genetic reduction of V-ATPase activity significantly reduces migration of invasive tumor cells in vitro. Importantly, the V-ATPase inhibitor archazolid abrogates tumor dissemination in a syngeneic mouse 4T1 breast tumor metastasis model. Pretreatment of cancer cells with archazolid impairs directional motility by preventing spatially restricted, leading edge localization of epidermal growth factor receptor (EGFR) as well as of phosphorylated Akt. Archazolid treatment or silencing of V-ATPase inhibited Rac1 activation, as well as Rac1-dependent dorsal and peripheral ruffles by inhibiting Rab5-mediated endocytotic/exocytotic trafficking of Rac1. The results indicate that archazolid effectively decreases metastatic dissemination of breast tumors by impairing the trafficking and spatially restricted activation of EGFR and Rho-GTPase Rac1, which are pivotal for directed movement of cells. Thus, our data reveals a novel mechanism underlying the role of V-ATPase in tumor dissemination
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban ACTIVATION article Cells EGFR Epidermal Growth Factor EPIDERMAL-GROWTH-FACTOR GROWTH In Vitro Metastasis mouse Movement Research Research Support Support TUMORS
Megjelenés:	Cancer Research. - 72 : 22 (2012), p. 5976-5987. -
További szerzők:	Schwarzenberg, Karin von Palamidessi, Andrea Schreiner, Laura Kubisch, Rebekka Liebl, Johanna Schempp, Christina Trauner, Dirk Vereb György (1965-) (biofizikus, orvos) Zahler, Stefan Wagner, Ernst Müller, Rolf Scita, Giorgio Vollmar, Angelika M.
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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