The Interplay of Tumor Stroma and Translational Factors in Endometrial Cancer

Sobočan, Monika; Smolle, Maria Anna; Schatz, Christoph; Haybaeck, Johannes

doi:10.3390/cancers12082074

Cited by 12 publications

(6 citation statements)

References 77 publications

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“…More specifically, TGF-β is increased in adenomyotic lesions and leads to EMT [ 1 ], possibly by activating mTORC2, one of its main downstream targets in this process [ 69 ]. In addition, the PI3K/AKT/mTOR pathway stimulates TWIST, a transcription factor that promotes the EMT phenotype in endometrial cells [ 12 ]. Finally, the protein kinase FAK may mediate EMT in adenomyosis via activation of the PI3K/AKT signaling cascade [ 70 ].…”

Section: Mtor and Eif Signaling In Benign Endometrial Diseasesmentioning

confidence: 99%

“…Current knowledge about their biological background brings the role of the mammalian target of the rapamycin (mTOR) signaling pathway to the fore. In fact, aside from its well-known importance in malignant endometrial disorders [ 11 , 12 , 13 ], mTOR signaling and its associated eukaryotic translation initiation factors (eIFs) seem to play a critical role in the development of non-cancerous endometrial diseases as well. The purpose of this review is to illuminate the involvement of mTOR signaling in the pathogenesis of adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia and to address its potential as a therapeutic target for these conditions.…”

Section: Introductionmentioning

confidence: 99%

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The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Driva

Schatz

Sobočan

et al. 2022

IJMS

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Adenomyosis, endometriosis, endometritis, and typical endometrial hyperplasia are common non-cancerous diseases of the endometrium that afflict many women with life-impacting consequences. The mammalian target of the rapamycin (mTOR) pathway interacts with estrogen signaling and is known to be dysregulated in endometrial cancer. Based on this knowledge, we attempt to investigate the role of mTOR signaling in benign endometrial diseases while focusing on how the interplay between mTOR and eukaryotic translation initiation factors (eIFs) affects their development. In fact, mTOR overactivity is apparent in adenomyosis, endometriosis, and typical endometrial hyperplasia, where it promotes endometrial cell proliferation and invasiveness. Recent data show aberrant expression of various components of the mTOR pathway in both eutopic and ectopic endometrium of patients with adenomyosis or endometriosis and in hyperplastic endometrium as well. Moreover, studies on endometritis show that derangement of mTOR signaling is linked to the establishment of endometrial dysfunction caused by chronic inflammation. This review shows that inhibition of the mTOR pathway has a promising therapeutic effect in benign endometrial conditions, concluding that mTOR signaling dysregulation plays a critical part in their pathogenesis.

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Section: Mtor and Eif Signaling In Benign Endometrial Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Driva

Schatz

Sobočan

et al. 2022

IJMS

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“…Astrocyte-elevated gene-1 induced gastric cancer metastasis by upregulation of eIF4E expression (34). In addition, eIF4E can be used as a therapeutic target for ovarian cancer, prostate cancer, lung cancer and other cancers, and the eIF4E-directed therapies LY2275796 (anti-sense oligonucleotides directed against eIF4E) and ribavirin (which reduces eIF4E-dependent translation) are already in clinical trials (35)(36)(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Decreased microRNA‑768‑3p expression indicates a poor prognosis in patients with breast cancer and promotes breast cancer cell viability, migration and invasion

Zhou

Wang

et al. 2021

Oncol Lett

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Breast cancer is the most common malignancy in women and microRNA-768-3p (miR-768-3p) is abnormally expressed in hepatocellular carcinoma, non-small cell lung carcinomas and melanoma. The aim of the present study was to evaluate the prognostic value and biological function of miR-768-3p in breast cancer. The expression of miR-768-3p in tumor tissues and adjacent tissues of 116 patients with breast cancer obtained by surgery and normal breast cell lines MCF-10A and breast cancer cell lines (MCF-7, MDA-MB-231, T-47D and SK-BR-3) were detected by reverse transcription-quantitative PCR. The association between miR-768-3p expression and the clinicopathological characteristics of patients was analyzed using the χ 2 test. In addition, the Kaplan-Meier method was used for survival analysis. A Cox regression model was used to examine the effect of miR-768-3p on the prognosis of patients with breast cancer. Hemocytometer cell counting and Transwell assays were used to detect the effects of miR-768-3p on the characteristics of breast cancer cells. The target genes of miR-768-3p in breast cancer were identified by bioinformatics software and detected by luciferase reporter assay. Compared with normal tissues and normal breast cancer cells, miR-768-3p was significantly decreased in breast cancer tissues and cancer cells (P<0.001). The reduction in miR-768-3p was significantly associated with lymph node metastasis (P=0.040), Tumor Node Metastasis stage (P=0.035), and cancer subtype (P=0.008). In addition, patients with low miR-768-3p expression had a shorter overall survival time (log-rank P=0.022) compared with those with high expression and miR-768-3p may be a potential prognostic marker (hazard ratio=4.637; 95% confidence interval=1.296-16.597; P=0.018). When transfected with miR-768-3p inhibitor, cell viability, migration and invasion were significantly promoted compared with the control group (P<0.05). In addition, eukaryotic translation initiation factor 4E (eIF4E) was the target gene of miR-768-3p in breast cancer. All experiments confirmed that miR-768-3p, a tumor suppressor, inhibited the viability, migration and invasion of breast cancer cells through eIF4E. miR-768-3p may be a potential prognostic marker of breast cancer and may participate in the progression of breast cancer.

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“…Both mTOR pathway and Wnt signalling have been linked to EMT process. Identifying key molecules of those pathways can contribute to improvement of targeted treatment options [ 62 ]. Another perspective biomarkers is ARID1A , a tumour suppressor gene encoding a large nuclear protein, involved in chromatin remodelling [ 63 ].…”

Section: Clinical Significance Of Ctnnb1 Mutationsmentioning

confidence: 99%

The Role of CTNNB1 in Endometrial Cancer

2022

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Endometrial cancer (EC) is the most common gynaecologic malignancy in the developed countries. Recent evidence suggests that histopathological subtyping together with molecular subgrouping can lead to more accurate assessment of the risk profile for the patient. Clinical studies suggest the currently used molecular classification improves the risk assessment of women with endometrial cancer but does not explain the differences in recurrence profiles clearly. This could be improved by novel markers. One of such are mutations in the β-catenin (CTNNB1) gene, a frequently mutated gene in endometrial cancer. This shows mutations mostly at phosphorylation sites of the β-catenin and almost exclusively in the endometrial subgroup of no specific molecular profile. CTNNB1 mutations lead to alterations in the Wnt/β-catenin signalling pathway, involved in the carcinogenesis and progression of EC by inducing transcription of target genes, whose function is to regulate the cell cycle. Although tumours with mutations in CTNNB1 tend to have low-risk characteristics, they are related to worse outcomes with significantly increased rate of disease recurrence and lower overall survival.

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The Interplay of Tumor Stroma and Translational Factors in Endometrial Cancer

Cited by 12 publications

References 77 publications

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

The Role of mTOR and eIF Signaling in Benign Endometrial Diseases

Decreased microRNA‑768‑3p expression indicates a poor prognosis in patients with breast cancer and promotes breast cancer cell viability, migration and invasion

The Role of CTNNB1 in Endometrial Cancer

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