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- W1888332220 abstract "Abstract : Our patch clamp studies indicate MscCa is expressed by the invasive prostate tumor cell PC-3. Anti-MscCa agents, Gd3+, GsmTx-4, and an anti-TRPC1 antibody block PC-3 cell migration. MscCa activity can be recorded over the surface of the PC-3 cell but is expressed at higher density on the rear compared with the front of the cell. This channel density gradient combined with a higher density of thapsigargin-sensitive Ca2+ stores in the rear of the cell enables the development of an intracellular Ca2+ gradient (low front ?high rear) in migrating PC-3 cells that determines migration directionality. Gene silencing of TRPC1 and/or TRPC3, but not TRPC4 or TRPC6, blocks PC-3 cell migration. Permanently suppressing TRPC1 also reduces PC-3 cell proliferation and thereby blocks tumor invasion in vivo. The non-invasive human prostate tumor cell line LNCaP expresses MscCa but the channel undergoes rapid inactivation that prevents Ca2+ gradient development and directional cell migration. Our results indicate that specific forms of mechanical stimuli can switch the inactivating gating mode to the non-inactivating mode seen in PC-3 cells, and this switch is independent of the actin-cytoskeleton. These findings have specific implications regarding the possible role of the increases mechanical forces (e.g., solid stress and interstitial fluid compression) that develop within a growing prostate tumor in promoting its progression to malignancy." @default.
- W1888332220 created "2016-06-24" @default.
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- W1888332220 date "2008-01-01" @default.
- W1888332220 modified "2023-09-25" @default.
- W1888332220 title "The Mechanosensory Ca2+ Channel as a Central Regulator of Prostate Tumor Cell Migration and Invasiveness" @default.
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- W1888332220 doi "https://doi.org/10.21236/ada480063" @default.
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