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TGF?-induced epithelial-to-mesenchymal transition in prostate cancer cells is
mediated via TRPM7 expression
#MMPMID29500887
Sun Y
; Schaar A
; Sukumaran P
; Dhasarathy A
; Singh BB
Mol Carcinog
2018[Jun]; 57
(6
): 752-761
PMID29500887
show ga
Growth factors, such as the transforming growth factor beta (TGF?), play an
important role in promoting metastasis of prostate cancer, thus understanding how
TGF? could induce prostate cancer cell migration may enable us to develop
targeted strategies for treatment of advanced metastatic prostate cancer. To more
clearly define the mechanism(s) involved in prostate cancer cell migration, we
undertook a series of studies utilizing non-malignant prostate epithelial cells
RWPE1 and prostate cancer DU145 and PC3 cells. Our studies show that increased
cell migration was observed in prostate cancer cells, which was mediated through
epithelial-to-mesenchymal transition (EMT). Importantly, addition of Mg(2+) , but
not Ca(2+) , increased cell migration. Furthermore, TRPM7 expression, which
functions as an Mg(2+) influx channel, was also increased in prostate cancer
cells. Inhibition of TRPM7 currents by 2-APB, significantly blocked cell
migration in both DU145 and PC3 cells. Addition of growth factor TGF? showed a
further increase in cell migration, which was again blocked by the addition of
2-APB. Importantly, TGF? addition also significantly increased TRPM7 expression
and function, and silencing of TRPM7 negated TGF?-induced cell migration along
with a decrease in EMT markers showing loss of cell adhesion. Furthermore,
resveratrol, which decreases prostate cancer cell migration, inhibited TRPM7
expression and function including TGF?-induced cell migration and activation of
TRPM7 function. Together, these results suggest that Mg(2+) influx via TRPM7
promotes cell migration by inducing EMT in prostate cancer cells and resveratrol
negatively modulates TRPM7 function thereby inhibiting prostate cancer
metastasis.
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