Soluble guanylyl cyclase α1 subunit is a key mediator of proliferation, survival, and migration in ECC-1 and HeLa cell lines

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 on these subunits by increasing α1 and decreasing both β1 expression and enzymatic activity. To date, the physiological relevance...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2019-10, Vol.9 (1), p.14797-11, Article 14797
Main Authors: Ronchetti, Sonia A, Pino, María Teresa L, Cordeiro, Georgina, Bollani, Sabrina N, Ricci, Analía G, Duvilanski, Beatriz H, Cabilla, Jimena P
Format: Article
Language:English
Subjects:
17β-Estradiol
Apoptosis
Cell adhesion & migration
Cell death
Cell growth
Cell migration
Cell Movement - physiology
Cell proliferation
Cell Proliferation - physiology
Cell survival
Cell Survival - physiology
Cervical cancer
Cervix
Endometrial cancer
Endometrial Neoplasms - pathology
Endometrium
Enzymatic activity
Estradiol - metabolism
Female
Gene Knockdown Techniques
Guanylate cyclase
HeLa Cells
Humans
Menopause
Receptors, Estrogen - metabolism
Soluble Guanylyl Cyclase - genetics
Soluble Guanylyl Cyclase - metabolism
Tumor cell lines
Tumors
Up-Regulation
Uterine Cervical Neoplasms - pathology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 on these subunits by increasing α1 and decreasing both β1 expression and enzymatic activity. To date, the physiological relevance of E2-induced sGC subunits' imbalance has not been addressed. Also, increased levels strongly correlate with E2-induced proliferation in E2-dependent tissues. The aim of the present study was to investigate the role of sGCα1 in proliferation, survival, and migration in two E2-responsive and non-responsive tumour cell lines. Here we showed that E2 stimulated sGCα1 expression in ECC-1 endometrial cancer cells. sGCα1 knock-down significantly reduced E2-dependent cell proliferation. Moreover, sGCα1 silencing caused G1 arrest together with an increase in cell death and dramatically inhibited cell migration. Surprisingly, disruption of sGCα1 expression caused a similar effect even in absence of E2. Confirming this effect, sGCα1 knock-down also 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 in ECC-1 and HeLa cells and suggest that sGCα1 can not only mediate E2-tumour promoting effects but can also be involved in hormone-independent tumour progression.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-51420-5