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GLP1R inhibits the progression of endometrial carcinoma through activation of cAMP/PKA pathway
Wu Li1, Yanpin Gu1, Songjun Liu1
1Department of Gynaecology, Tongde Hospital of Zhejiang Province, Hangzhou, China.
Background:
This study strived to explore the role and mechanism of glucagon-like peptide-1 receptor (GLP1R) in endometrial carcinoma (EC).
Methods:
In detail, after transfection of GLP1R overexpression vector and small interfering RNA targeting PKA, the mRNA expressions of GLP1R and PKA in EC cells (Ishikawa and RL95-2) were quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The cell biological behaviors, including proliferation, migration, invasion, and apoptosis, were detected using 5-ethynyl-2'-deoxyuridine (EdU), wound healing, transwell, and flow cytometry assays, respectively. The cyclic adenosine monophosphate (cAMP) content and related protein expressions (GLP1R, p-PKA, and PKA) were determined by enzyme-linked immunosorbent assay (ELISA) and western blot. The effects of GLP1R and PKA on tumorigenesis were evaluated by measuring the tumor volume and weight of mice bearing EC.
Result:
According to the results, GLP1R expression was downregulated in EC tissues and cells, and there was a positive correlation between GLP1R and PKA expressions. Upregulation of GLP1R promoted apoptosis and activated the cAMP/PKA signaling pathway in EC cells, while hindering the EC cell proliferation, invasion, migration, and the growth of tumor in mice. However, these effects were blunted by downregulation of PKA, which also accelerated the progression of EC in vitro and in vivo via inhibiting the activation of cAMP/PKA signaling pathway.
Conclusion:
Collectively, upregulation of GLP1R impeded EC progression via inducing the activation of cAMP/PKA signaling pathway, which may be a potential treatment for EC.
Insights
Upregulating glucagon-like peptide-1 receptor (GLP1R) inhibits endometrial carcinoma (EC) progression by activating the cAMP/PKA pathway. This suggests GLP1R as a potential therapeutic target for EC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Endometrial carcinoma (EC) is a significant gynecological malignancy.
- The role and underlying mechanisms of glucagon-like peptide-1 receptor (GLP1R) in EC remain underexplored.
Purpose of the Study:
- To investigate the functional role of GLP1R in endometrial carcinoma.
- To elucidate the molecular mechanism by which GLP1R influences EC progression.
- To evaluate GLP1R as a potential therapeutic target for EC.
Main Methods:
- Gene expression analysis of GLP1R and PKA in EC cells using qRT-PCR.
- Assessment of EC cell behaviors (proliferation, migration, invasion, apoptosis) via EdU, wound healing, Transwell, and flow cytometry assays.
- Determination of cAMP levels and protein expression (GLP1R, PKA) using ELISA and Western blot; in vivo tumorigenesis evaluation in mice.
Main Results:
- GLP1R expression was found to be downregulated in EC tissues and cells.
- Upregulation of GLP1R promoted apoptosis and inhibited EC cell proliferation, migration, and invasion by activating the cAMP/PKA pathway.
- Downregulation of PKA blunted the anti-tumor effects of GLP1R, accelerating EC progression both in vitro and in vivo.
Conclusions:
- GLP1R upregulation impedes EC progression through the activation of the cAMP/PKA signaling pathway.
- GLP1R represents a promising therapeutic target for endometrial carcinoma.
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