Response to Letter Regarding Article, “Effects of Sildenafil on Ventricular and Vascular Function in Heart Failure With Preserved Ejection Fraction”. full article pdf download

Title of article - Response to Letter Regarding Article, “Effects of Sildenafil on Ventricular and Vascular Function in Heart Failure With Preserved Ejection Fraction”.

Abstract

The incidence of malignant melanoma, a cancer of the melanocyte cell lineage, has nearly doubled in the past 20 years. Wnt5A, akey driver of melanoma invasiveness, induces Ca2 signals. To understand how store-operated calcium entry (SOCE) contributes to Wnt5A-induced malignancy in melanoma models, we examined the expression and function of STIM1 and Orai1 in patient-derived malignant melanoma cells, previously characterized as either highly invasive (metastatic) or noninvasive. Using both fluorescence microscopy and electrophysiological approaches, we show that SOCE is greatly diminished in invasive melanoma compared to its level in noninvasive cell types. However, no loss of expression of any members of the STIM and Orai families was observed in invasive melanoma cells. Moreover, overexpressed wild-type STIM1 and Orai1 failed to restore SOCE in invasive melanoma cells, and we observed no defects in their localization before or after store depletion in any of the invasive celllines. Importantly, however, we determined that SOCE was restored by inhibition of protein kinase C, a known downstream target of Wnt5A. Furthermore, coexpression of STIM1 with an Orai1 mutant insensitive to protein kinase C-mediated phosphorylation fully restored SOCE in invasive melanoma. These findings reveal a level of control for STIM/Orai function in invasive melanoma not previously reported.

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Details of Journal for Response to Letter Regarding Article, “Effects of Sildenafil on Ventricular and Vascular Function in Heart Failure With Preserved Ejection Fraction”.

Journal Title - Circulation. Heart failure

ISSN - 1941-3297

Volume - 8

Issue - 4

Publish date - 2015-Jul

Language - eng

Country - United States