KCNA1 and TRPC6 ion channels and NHE1 exchanger operate the biological outcome of HGF/scatter factor in renal tubular cells

Rampino, Teresa; Gregorini, Marilena; Guidetti, Cristina; Broggini, Massimo; Marchini, Sergio; Bonomi, Riccardo; Maggio, Milena; Roscini, Elisabetta; Soccio, Grazia; Tiboldo, Renza; Canton, Antonio Dal

doi:10.1080/08977190801892184

Cited by 25 publications

(21 citation statements)

References 47 publications

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“…This suggests that the number of channels in the plasma membrane increases, rather than that existing channels alter their conductance properties. Second, high-frequency influx events occur through all channel types in the membranes of MDCK cells, consistent with the observation that HGF signaling has been shown to trigger ion channel fluxes generally, including through TrpC6, perhaps explaining why a number of ion channel blockers have been shown to block HGF signaling (Jin et al, 2003;Rampino et al, 2007;Wang et al, 2010). This indicates that regulation of channel activity at the membrane is not specific to channel type, as would be expected in the case of vesicle delivery.…”

Section: Trpc6 Function In Hgf-induced Epithelial Scatteringsupporting

confidence: 57%

“…In glioblastoma, it is TrpM8 that increases cytosolic calcium concentration in response to HGF treatment (Wondergem et al, 2008). In HK2 cells, a renal tubular epithelial cell line, TrpC6 is required for HGF-induced proliferation, migration, and actin rearrangements (Rampino et al, 2007). Further, exogenous overexpression of the calcium channel polycystin-1 in MDCK cells drives scattering (Boca et al, 2007), suggesting that calcium influxes play a role in EMT.…”

Section: Trpc6 Function In Hgf-induced Epithelial Scatteringmentioning

confidence: 99%

“…Importantly, that TrpC6 is required for HGF-induced scattering does not preclude other channels from also being required for EMT, though perhaps in different branches of the HGF signaling network. Though there is evidence that ion channels play a general role in cellular processes downstream of HGF (Jin et al, 2003;Rampino et al, 2007), we propose that calcium influxes through specific channels are connected to specific downstream signaling events. Activation of multiple calcium channels, each tied to distinct downstream signaling events, could facilitate selective and independent activation of multiple downstream effectors.…”

Section: Trpc6 Function In Hgf-induced Epithelial Scatteringmentioning

confidence: 99%

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Plasma membrane ion fluxes and NFAT-dependent gene transcription contribute to c-met-induced epithelial scattering

Langford

Keyes

Hansen

2012

Journal of Cell Science

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SummaryHepatocyte growth factor (HGF) signaling drives epithelial cells to scatter by breaking cell-cell adhesions and causing them to migrate as solitary cells, a process that parallels epithelial-mesenchymal transition. HGF binds and activates the c-met receptor tyrosine kinase, but downstream signaling required for scattering remains poorly defined. We have applied a chemical biology approach to identify components of HGF signaling that are required for scattering in an in vitro model system. This approach yields a number of small molecules that block HGF-induced scattering, including a calcium channel blocker. We show that HGF stimulation results in sudden and transient increases in ion channel influxes at the plasma membrane. Although multiple channels occur in the membranes of our model system, we find that TrpC6 is specifically required for HGF-induced scattering. We further demonstrate that HGF-induced ion influxes through TrpC6 channels coincide with a transient increase in nuclear factor of activated T-cells (NFAT)-dependent gene transcription and that NFAT-dependent gene transcription is required for HGF-induced cell scattering.

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Section: Trpc6 Function In Hgf-induced Epithelial Scatteringsupporting

confidence: 57%

Section: Trpc6 Function In Hgf-induced Epithelial Scatteringmentioning

confidence: 99%

Section: Trpc6 Function In Hgf-induced Epithelial Scatteringmentioning

confidence: 99%

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Plasma membrane ion fluxes and NFAT-dependent gene transcription contribute to c-met-induced epithelial scattering

Langford

Keyes

Hansen

2012

Journal of Cell Science

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“…HGF-induced Ca 2+ oscillations are observed in hepatocytes [15]. HGF induces epithelial tubular cell proliferation, migration, scattering and tubulogenesis through KCNA1, TRPC6 and NHE1 [16]. In addition, El Boustany et al [9] found that endothelial growth factor (EGF) and HGF increase TRPC6 levels and induce a large increase in store-operated calcium entry amplitude in Huh-7 cells.…”

Section: Introductionmentioning

confidence: 99%

The role of TRPC6 in HGF-induced cell proliferation of human prostate cancer DU145 and PC3 cells

Wang¹,

Yue²,

Li³

et al. 2010

Asian J Androl

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Hepatocyte growth factor (HGF) is a glycoprotein that induces prostate cancer cell proliferation, migration and invasion. The activation of transient receptor potential canonical 6 (TRPC6) channels is considered important in promoting prostate cancer cell proliferation. In this study, we assessed the role of endogenous TRPC6 channels in the HGF-induced cell proliferation of prostate cancer. Reverse transcription-PCR and Western blotting were used to investigate TRPC6 expression. Electrophysiological techniques (whole-cell patch clamp configuration) and Ca 2+ imaging analysis were used to investigate the channel activity in cells. The effects of TRPC6 channels on cell cycle progression, cell apoptosis and cell growth were also examined. TRPC6 and c-MET were expressed in DU145 and PC3 cells. In addition, functional TRPC6 channels were present in DU145 and PC3 cells, and TRPC6 knockdown suppressed TRPC-like currents evoked by oleoyl-2-acetyl-sn-glycerol (OAG). Inhibition of TRPC6 channels in DU145 and PC3 cells abolished OAG-and HGF-induced Ca 2+ entry. Furthermore, inhibition of TRPC6 channels arrested DU145 and PC3 cells at the G2/M phase and suppressed HGF-induced cell proliferation. Collectively, our results indicate that TRPC6 has an important role in HGF-induced DU145 and PC3 cell proliferation.

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“…36 TRPC6 inhibitors prevent HGFinduced proliferation, migration, and morphogenesis of HK2 cells. 37 Additionally, Langford et al 31 concluded that TRPC6 is specifically required for HGFinduced scattering in MDCK cells, though calcium fluxes through TRPV4 and other channels are all increased at the plasma membrane following HGF stimulation.…”

Section: The Case For Intracellular Calciummentioning

confidence: 99%

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

2016

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Epithelial tissues use adherens junctions to maintain tight interactions and coordinate cellular activities. Adherens junctions are remodeled during epithelial morphogenesis, including instances of epithelialmesenchymal transition, or EMT, wherein individual cells detach from the tissue and migrate as individual cells. EMT has been recapitulated by growth factor induction of epithelial scattering in cell culture. In culture systems, cells undergo a highly reproducible series of cell morphology changes, most notably cell spreading followed by cellular compaction and cell migration. These morphology changes are accompanied by striking actin rearrangements. The current evidence suggests that global changes in actomyosin-based cellular contractility, first a loss of contractility during spreading and its activation during cell compaction, are the main drivers of epithelial scattering. In this review, we focus on how spreading and contractility might be controlled during epithelial scattering. While we propose a central role for RhoA, which is well known to control cellular contractility in multiple systems and whose role in epithelial scattering is well accepted, we suggest potential roles for additional cellular systems whose role in epithelial cell biology has been less well documented. In particular, we propose critical roles for vesicle recycling, calcium channels, and calcium-dependent kinases.

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KCNA1 and TRPC6 ion channels and NHE1 exchanger operate the biological outcome of HGF/scatter factor in renal tubular cells

Cited by 25 publications

References 47 publications

Plasma membrane ion fluxes and NFAT-dependent gene transcription contribute to c-met-induced epithelial scattering

Plasma membrane ion fluxes and NFAT-dependent gene transcription contribute to c-met-induced epithelial scattering

The role of TRPC6 in HGF-induced cell proliferation of human prostate cancer DU145 and PC3 cells

Control of cell mechanics by RhoA and calcium fluxes during epithelial scattering

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