ArticleBMC cancer2013
Gonadotropin-releasing hormone type II (GnRH-II) agonist regulates the invasiveness of endometrial cancer cells through the GnRH-I receptor and mitogen-activated protein kinase (MAPK)-dependent activation of matrix metalloproteinase (MMP)-2.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Article
- Kisspeptin Regulates Cell Invasion and Migration in Endometrial Cancer.Journal of the Endocrine Society · 2024Article
- Gonadotropin-Releasing Hormone Antagonists-A New Hope in Endometriosis Treatment?Journal of clinical medicine · 2023Review
- Role of gonadotropin-releasing hormone 2 and its receptor in human reproductive cancers.Frontiers in endocrinology · 2023Review
- The role of GnRH metabolite, GnRH-(1-5), in endometrial cancer.Frontiers in endocrinology · 2023Review
- Review
- Kisspeptin regulation of human decidual stromal cells motility via FAK-Src intracellular tyrosine kinases.Human reproduction (Oxford, England) · 2019Article
- Fertility Sparing Treatment in Patients With Early Stage Endometrial Cancer, Using a Combination of Surgery and GnRH Agonist: A Monocentric Retrospective Study and Review of the Literature.Frontiers in medicine · 2018Article
- Preliminary clinical application of an aromatase inhibitor and a gonadotropin-releasing hormone agonist combination for inoperable endometrial cancer patients with comorbidities: case report and literature review.Cancer biology & therapy · 2018Article
- GnRH-(1-5) Inhibits TGF-β Signaling to Regulate the Migration of Immortalized Gonadotropin-Releasing Hormone Neurons.Frontiers in endocrinology · 2018Article
- GnRH-(1-5) transactivates EGFR in Ishikawa human endometrial cells via an orphan G protein-coupled receptor.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Apoptotic death of prostate cancer cells by a gonadotropin-releasing hormone-II antagonist.PloS one · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMore than 25% of patients diagnosed with endometrial carcinoma have an invasive primary cancer accompanied by metastases. Gonadotropin-releasing hormone (GnRH) plays an important role in reproduction. In mammals, expression of GnRH-II is higher than GnRH-I in reproductive tissues. Here, we examined the effect of a GnRH-II agonist on the motility of endometrial cancer cells and its mechanism of action in endometrial cancer therapy.
methodsImmunoblotting and immunohistochemistry (IHC) were used to determine the expression of the GnRH-I receptor protein in human endometrial cancer. The activity of MMP-2 in the conditioned medium was determined by gelatin zymography. Cell motility was assessed by invasion and migration assay. GnRH-I receptor si-RNA was applied to knockdown GnRH-I receptor.
resultsThe GnRH-I receptor was expressed in the endometrial cancer cells. The GnRH-II agonist promoted cell motility in a dose-dependent manner. The GnRH-II agonist induced the phosphorylation of ERK1/2 and JNK, and the phosphorylation was abolished by ERK1/2 inhibitor (U0126) and the JNK inhibitor (SP600125). Cell motility promoted by GnRH-II agonist was suppressed in cells that were pretreated with U0126 and SP600125. Moreover, U0126 and SP600125 abolished the GnRH-II agonist-induced activation of MMP-2. The inhibition of MMP-2 with MMP-2 inhibitor (OA-Hy) suppressed the increase in cell motility in response to the GnRH-II agonist. Enhanced cell motility mediated by GnRH-II agonist was also suppressed by the knockdown of the endogenous GnRH-I receptor using siRNA.
conclusionOur study indicates that GnRH-II agonist promoted cell motility of endometrial cancer cells through the GnRH-I receptor via the phosphorylation of ERK1/2 and JNK, and the subsequent, MAPK-dependent activation of MMP-2. Our findings represent a new concept regarding the mechanism of GnRH-II-induced cell motility in endometrial cancer cells and suggest the possibility of exploring GnRH-II as a potential therapeutic target for the treatment of human endometrial cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.