title: Mechanosensitive Ca(2+) permeant cation channels in human prostate tumor cells.
abstract: The acquisition of cell motility plays a critical role in the spread of prostate cancer (PC), therefore, identifying a sensitive step that regulates PC cell migration should provide a promising target to block PC metastasis. Here, we report that a mechanosensitive Ca(2+)-permeable cation channel (MscCa) is expressed in the highly migratory/invasive human PC cell line, PC-3 and that inhibition of MscCa by Gd(3+) or GsMTx-4 blocks PC-3 cell migration and associated elevations in [Ca(2+)](i). Genetic suppression or overexpression of specific members of the canonical transient receptor potential Ca(2+) channel family (TRPC1 and TRPC3) also inhibit PC-3 cell migration, but they do so by mechanisms other that altering MscCa activity. Although LNCaP cells are nonmigratory, they also express relatively large MscCa currents, indicating that MscCa expression alone cannot confer motility on PC cells. MscCa in both cell lines show similar conductance and ion selectivity and both are functionally coupled via Ca(2+) influx to a small Ca(2+)-activated K(+) channel. However, MscCa in PC-3 and LNCaP cell patches show markedly different gating dynamics--while PC-3 cells typically express a sustained, non-inactivating MscCa current, LNCaP cells express a mechanically-fragile, rapidly inactivating MscCa current. Moreover, mechanical forces applied to the patch, can induce an irreversible transition from the transient to the sustained MscCa gating mode. Given that cancer cells experience increasing compressive and shear forces within a growing tumor, a similar shift in channel gating in situ would have significant effects on Ca(2+) signaling that may play a role in tumor progression.
authors.affiliation: Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Rosario
authors.initials: R
authors.lastname: Maroto
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurosky
authors.forename: Owen P
authors.initials: OP
authors.lastname: Hamill
mesh_terms: D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D013111:Spider Venoms / Q000494:pharmacology; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; C411249:MTx4 protein, Grammostola spatulata; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D034741:RNA, Small Interfering; D013111:Spider Venoms; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C096351:transient receptor potential cation channel, subfamily C, member 1; D005682:Gadolinium; D002118:Calcium