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2017 ; 7
(1
): 14199
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English Wikipedia
Ca(2+) protein alpha 1D of CaV1 3 regulates intracellular calcium concentration
and migration of colon cancer cells through a non-canonical activity
#MMPMID29079724
Fourbon Y
; Guéguinou M
; Félix R
; Constantin B
; Uguen A
; Fromont G
; Lajoie L
; Magaud C
; Lecomte T
; Chamorey E
; Chatelier A
; Mignen O
; Potier-Cartereau M
; Chantôme A
; Bois P
; Vandier C
Sci Rep
2017[Oct]; 7
(1
): 14199
PMID29079724
show ga
It is generally accepted that voltage-gated Ca(2+) channels, CaV, regulate Ca(2+)
homeostasis in excitable cells following plasma membrane depolarization. Here, we
show that the Ca(2+) protein ?1D of CaV1.3 channel is overexpressed in colorectal
cancer biopsies compared to normal tissues. Gene silencing experiments targeting
?1D reduced the migration and the basal cytosolic Ca(2+) concentration of HCT116
colon cancer cell line and modified the cytosolic Ca(2+) oscillations induced by
the sodium/calcium exchanger NCX1/3 working in its reverse mode. Interestingly,
NCX1/3 regulated membrane potential of HCT116 cells only when ?1D was silenced,
and blocking NCX1/3 increased cytosolic Ca(2+) concentration and cell migration.
However, membrane depolarization did not induce an increase in intracellular
Ca(2+). Patch-clamp experiments clearly showed that the inward Ca(2+) current was
absent. Finally, flow cytometry and immunofluorescence studies showed that ?1D
protein was localized at the plasma membrane, in cytosol and cell nuclei.
Altogether, we uncover a novel signaling pathway showing that ?1D is involved in
the regulation of Ca(2+) homeostasis and cell migration by a mechanism
independent of its plasma membrane canonical function but that involved plasma
membrane Na(+)/Ca(2+) exchanger.