Notch signalling and voltage-gated Na+ channel activity in human prostate cancer cells: independent modulation of in vitro motility.
This study tested the possible functional relationship of two signalling mechanisms shown previously to be involved in human prostate cancer (PCa), Notch and voltage-gated sodium channel. Notch1 and Notch2 were differentially expressed in PCa cell lines of varying metastatic potential (LNCaP, PC-3, PC-3M) in comparison to a normal prostate cell line (PNT2), whereas Notch3 and Notch4 were not expressed. The Notch ligand Jagged1, but not Jagged2, was increased in all cell lines, whereas the Notch downstream target Deltex was not expressed. In comparison to the LNCaP cell line, Hes1, another downstream target, showed elevated expression in the metastatic PC-3 and PC-3M cells and promoted lateral motility. In contrast, the Notch ligand Delta-like1 (Dll1) levels were higher in LNCaP compared with PC-3 and PC-3M cells. Importantly, decreasing Dll1 expression increased the lateral motility of PC-3 cells, whereas blocking voltage-gated Na(+) channel activity with tetrodotoxin decreased motility. However, the effect of Dll1 was independent of Notch signalling through Hes1 and voltage-gated Na(+) channel expression/activity.
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Neuroscience Solutions to Cancer Research Group, Division of Cell and Molecular Biology, Imperial College London, South Kensington Campus, London, UK.
Fraser
S P
SP
Patel
P
P
Pridgeon
C
C
Dallman
M J
MJ
Djamgoz
M B A
MB
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D011042:Poisons / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism; D051883:Receptor, Notch2 / Q000378:metabolism; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D012997:Solvents / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D000072056:Transcription Factor HES-1; D014407:Tumor Cells, Cultured
D053829:Amyloid Precursor Protein Secretases; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D004121:Dimethyl Sulfoxide; D004791:Enzyme Inhibitors; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011042:Poisons; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D015222:Sodium Channels; D012997:Solvents; D013779:Tetrodotoxin; D000072056:Transcription Factor HES-1; C512941:DLK1 protein, human; C000606273:JAG1 protein, human; C497761:NOTCH1 protein, human; C497764:NOTCH2 protein, human; C499374:NOTCH3 protein, human; C106075:NOTCH4 protein, human; C078493:HES1 protein, human