Soluble guanylyl cyclase alpha 1 subunit is a key mediator of proliferation, survival, and migration in ECC-1 and HeLa cell lines.

PINO, MARIA TERESA L.; RICCI, ANALÍA GABRIELA; RONCHETTI, SONIA A.; BOLLANI, SABRINA; CABILLA, JIMENA P.; CORDEIRO, GEORGINA; DUVILANSKI, BEATRIZ H.

Scientific Reports

Springer Nature

Lugar: Londres; Año: 2019

Soluble guanylyl cyclase (sGC) is a heterodimeric enzyme constituted by two subunits,α1 and β1. Previously we have shown that 17β-estradiol (E2) exerts opposite effects onthese subunits by increasing α1 and decreasing both β1 expression and enzymaticactivity. To date, the physiological relevance of E2-induced sGC subunits? imbalancehas not been addressed. Also, increased levels strongly correlate with E2-inducedproliferation in E2-dependent tissues. The aim of the present study was to investigatethe role of sGCα1 in proliferation, survival, and migration in two E2-responsive andnon-responsive tumour cell lines.Here we showed that E2 stimulated sGCα1 expression in ECC-1 endometrial cancercells. sGCα1 knock-down significantly reduced E2-dependent cell proliferation.Moreover, sGCα1 silencing caused G1 arrest together with an increase in cell death anddramatically inhibited cell migration. Surprisingly, disruption of sGCα1 expressioncaused a similar effect even in absence of E2. Confirming this effect, sGCα1 knockdownalso augmented cell death and decreased proliferation and migration in E2-unresponsive HeLa cervical cancer cells.Our results show that sGCα1 mediated cell proliferation, survival, and migration inECC-1 and HeLa cells and suggest that sGCα1 can not only mediate E2-tumourpromoting effects but can also be involved in hormone-independent tumour progression.