Sterol Regulatory Element-Binding Protein–1/Fatty Acid Synthase Involvement in Proliferation Inhibition and Apoptosis Promotion Induced by Progesterone in Endometrial Cancer

Qiu, Chunping; Dongol, Samina; Lv, Qingqing; Gao, Xinying; Jiang, Jie

doi:10.1097/igc.0000000000000004

Cited by 16 publications

(10 citation statements)

References 22 publications

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“…With the development of lipidomics technology, accumulating evidence shows that abnormal lipid metabolism plays a dual role in tumorigenesis, specifically in the occurrence and development of cancers. Our research group focused on this field of EC in recent years, and the lipid metabolism‐related molecular markers include sterol regulatory element‐binding protein 1, sirtuins 1 and stearoyl‐CoA desaturase 1) . Previous research has confirmed that the energy supply of lipids comes from de novo synthesis rather than circulating lipids during tumor development .…”

Section: Discussionmentioning

confidence: 99%

Effect of monoacylglycerol lipase on the tumor growth in endometrial cancer

Gao

et al. 2019

J of Obstet and Gynaecol

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Aim Abnormal lipid metabolism plays a dual role in tumorigenesis, specifically in the occurrence and development of cancers. Monoacylglycerol lipase (MAGL), a hydrolase that is important for lipid metabolism, plays a vital role in different aspects of tumorigenesis. Many studies have shown that MAGL is highly elevated in a variety of cancers and plays an active role. However, its potential role in supporting endometrial cancer (EC) growth and progression has not yet been explored in depth. Methods Immunohistochemistry and quantitative real‐time reverse transcription polymerase chain reaction were performed to estimate the protein and messenger RNA (mRNA) levels of MAGL in tumor tissues. Then, JZL184 and small interfering RNA (siRNA) were used to decrease the expression of MAGL in EC cells. The gene and protein expression levels of MAGL were measured using quantitative real‐time PCR and western blotting, respectively. Additionally, the effect of MAGL on tumor growth in EC was detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide , cell cycle and western blotting assay in vitro. Results We found that MAGL was overexpressed in EC and was significantly correlated with surgical‐pathological stage, myometrial invasion, number of pregnancies and body mass index. The growth and cell cycle progression of tumor cells were significantly impaired in vitro by the pharmacological and siRNA‐mediated MAGL inhibition. In addition, MAGL inhibition seemed to repress two target genes, Cyclin D1 and Bcl‐2. Conclusion In summary, we have demonstrated that MAGL is involved in EC growth and progression. Our results suggest that targeting MAGL may be a novel and valid treatment for EC.

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Section: Discussionmentioning

confidence: 99%

Effect of monoacylglycerol lipase on the tumor growth in endometrial cancer

Gao

et al. 2019

J of Obstet and Gynaecol

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“…SREBP-1 functions as the key regulator of fatty acid metabolism by transcriptionally regulating the expression of these three lipogenic genes (5,14). Studies have demonstrated that SREBP-1 and FASN play crucial roles in the processes of EC oncogenesis and progression (10,27). ACL expression and activity are markedly increased in cancer cells, including EC cells, and ACL inhibition can suppress tumor cell growth (20,28).…”

Section: Discussionmentioning

confidence: 99%

Fatostatin suppresses growth and enhances apoptosis by blocking SREBP-regulated metabolic pathways in endometrial carcinoma

Gao

Shi

et al. 2018

Oncol Rep

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Fatostatin, a chemical inhibitor of the sterol regulatory element‑binding protein (SREBP) pathway, has been reported to possess high antitumor activity against prostate and pancreatic cancer. The main aim of the present study was to investigate the effects and mechanism of fatostatin in endometrial carcinoma (EC). In the present study, we determined that fatostatin inhibited EC cell viability and colony formation capacity, decreased the invasive and migratory capacities of EC cells, induced EC cell cycle arrest at the G2/M phase and stimulated caspase‑mediated apoptosis of EC cells. In addition, fatostatin significantly decreased the protein expression levels of nuclear SREBPs and their downstream genes and increased the protein expression levels of cleaved caspase‑9, caspase‑3 and PARP in EC cells. In addition, the mRNA expression levels of SREBP‑controlled downstream genes were also significantly downregulated. The quantification assays of fatty acids and total cholesterol revealed that the levels of free fatty acids and total cholesterol in EC cells were decreased. The present study indicated that fatostatin exhibited antitumor effects by blocking SREBP‑regulated metabolic pathways and inducing caspase‑mediated apoptosis in EC and may be a potent therapeutic strategy for the treatment of EC.

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“…This was attributed to an increased activation of sterol-regulatory-element- binding protein 1, a key regulator of lipogenic genes. Since this protein has been involved in the proliferation inhibition and apoptosis in endometrial cancer [25], it may be hypothesized that increased stearamide could be a response towards EC by healthy cells. In this line, EC cells could take profit by increasing endocanabinoid receptors.…”

Section: Discussionmentioning

confidence: 99%

Metabotyping human endometrioid endometrial adenocarcinoma reveals an implication of endocannabinoid metabolism

et al. 2016

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Metabolomics, an essential technique in precision medicine, contributes to the molecular fingerprinting of tumours, further helping to understand their pathogenesis. In this work, using a LC-ESI-QTOF-MS/MS platform, we demonstrated the existence of a specific metabolomic signature which could define endometrioid endometrial carcinoma (EEC), arising the endocannabinoid system as a potential pathway involved in EC pathogenesis. Metabolomics could also shed light in the processes involved in myometrial invasion, proposing new targets for possible therapeutic intervention. Consequently, we also described a different metabolomic profile in surface endometrioid carcinoma and myometrial invasive front. We validated pathways disclosed by metabolomics by immunohistochemistry. Specifically, endocannabinoid and purine metabolism could be involved in tumor myometrial invasion.

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Sterol Regulatory Element-Binding Protein–1/Fatty Acid Synthase Involvement in Proliferation Inhibition and Apoptosis Promotion Induced by Progesterone in Endometrial Cancer

Abstract: Sterol regulatory element-binding protein-1/FASN is involved in the proliferation suppression and apoptosis promotion brought about by MA in Ishikawa cells.

Cited by 16 publications

References 22 publications

Effect of monoacylglycerol lipase on the tumor growth in endometrial cancer

Effect of monoacylglycerol lipase on the tumor growth in endometrial cancer

Fatostatin suppresses growth and enhances apoptosis by blocking SREBP-regulated metabolic pathways in endometrial carcinoma

Metabotyping human endometrioid endometrial adenocarcinoma reveals an implication of endocannabinoid metabolism

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