Epithelial to mesenchymal transition in early stage endometrioid endometrial carcinoma

Endometrioid endometrial carcinoma (EEC), also known as type 1 endometrial cancer (EC), accounts for over 70–80% of all cases that are usually associated with estrogen stimulation and often develops in a background of atypical endometrial hyperplasia. The increased incidence of EC is mainly confined to this type of cancer. Most EEC patients present at an early stage and generally have a favorable prognosis; however, up to 30% of EEC present as high risk tumors, which have invaded deep into the myometrium at diagnosis and progressively lead to local or extra pelvic metastasis. The poor survival of advanced EC is related to the lack of effective therapies, which can be attributed to poor understanding of the molecular mechanisms underlying the progression of disease toward invasion and metastasis. Multiple lines of evidence illustrate that epithelial–mesenchymal transition (EMT)-like events are central to tumor progression and malignant transformation, endowing the incipient cancer cell with invasive and metastatic properties. The aim of this review is to summarize the current knowledge on molecular events associated with EMT in progression, invasion, and metastasis of EEC. Further, the role of epigenetic modifications and microRNA regulation, tumor microenvironment, and microcystic elongated and fragmented glands like invasion pattern have been discussed. We believe this article may perhaps stimulate further research in this field that may aid in identifying high risk patients within this clinically challenging patient group and also lead to the recognition of novel targets for the prevention of metastasis – the most fatal consequence of endometrial carcinogenesis.

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Prognostic implications of epithelial to mesenchymal transition related proteins (E-cadherin, Snail) and hypoxia inducible factor 1α in endometrioid endometrial carcinoma

Annals of Diagnostic Pathology ◽

10.1016/j.anndiagpath.2016.01.004 ◽

2016 ◽

Vol 22 ◽

pp. 1-11 ◽

Cited By ~ 13

Author(s):

Nehal S. Abouhashem ◽

Doaa Abdelaziz Ibrahim ◽

Abdel Motaleb Mohamed

Keyword(s):

Endometrial Carcinoma ◽

Epithelial To Mesenchymal Transition ◽

Hypoxia Inducible Factor ◽

Mesenchymal Transition ◽

Hypoxia Inducible Factor 1Α ◽

Endometrioid Endometrial Carcinoma ◽

Prognostic Implications ◽

Related Proteins ◽

E Cadherin

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Cathepsin B Is Upregulated and Mediates ECM Degradation in Colon Adenocarcinoma HT29 Cells Overexpressing Snail

Cells ◽

10.3390/cells8030203 ◽

2019 ◽

Vol 8 (3) ◽

pp. 203 ◽

Cited By ~ 12

Author(s):

Jakub Kryczka ◽

Izabela Papiewska-Pajak ◽

M. Anna Kowalska ◽

Joanna Boncela

Keyword(s):

Cathepsin B ◽

Epithelial To Mesenchymal Transition ◽

Early Stage ◽

Tumor Development ◽

Colon Adenocarcinoma ◽

Mesenchymal Cell ◽

Tissue Samples ◽

Mesenchymal Transition ◽

Colon And Rectum ◽

Phenotypic Shift

During tumor development and ongoing metastasis the acquisition of mesenchymal cell traits by epithelial carcinoma cells is achieved through a programmed phenotypic shift called the epithelial-to-mesenchymal transition, EMT. EMT contributes to increased cancer cell motility and invasiveness mainly through invadosomes, the adhesion structures that accompany the mesenchymal migration. The invadosomes and their associated proteases restrict protease activity to areas of the cell in direct contact with the ECM, thus precisely controlling cell invasion. Our data prove that Snail-overexpressing HT-29 cells that imitate the phenotype of colon cancer cells in the early stage of the EMT showed an increase in the expression and pericellular activity of cathepsin B. It appears that the pericellular localization of cathepsin B, also observed in colon and rectum adenocarcinoma tissue samples, plays a key role in its function.

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Early Development of The Trunk Neural Crest Cells in the Egyptian Cobra Naja H. Haje

10.21203/rs.3.rs-547365/v1 ◽

2021 ◽

Author(s):

Eraqi R. Khannoon ◽

Christian Alvarado ◽

Maria Elena Elena de Bellard

Keyword(s):

Embryonic Development ◽

Neural Crest ◽

Early Development ◽

Cancer Metastasis ◽

Epithelial To Mesenchymal Transition ◽

Early Stage ◽

Neural Crest Cells ◽

Migratory Behavior ◽

Mesenchymal Transition ◽

Trunk Neural Crest

Abstract Background: Trunk neural crest cells (TNCC) are representing a model for epithelial to mesenchymal transition, this correlates the importance of studying the migration of these cells to cancer metastasis. Reptiles are unique group of animals being very morphologically diverse and their close position to synapsid leading to mammals. Recently, more publications focused on the migratory behavior of trunk NCC during embryonic development of squamates. Only one colubrid snake has been studied so far regarding the NCC migration. Results: Here we follow the migratory behavior of TNCC with HNK1 in the elapid snake Naja h. haje from early stage to 14 days postoviposition. Comparing the colubrid snake with the Egyptian cobra showed that both snakes overall follow the same TNCC migratory pathways of both birds and mammals by following the rostral and avoiding the caudal portions of the somites. Conclusions: First, TNCC intra-somitic migration as observed in turtles supports a contributing role for TNCC to scale precursors. Second, our observation of significant numbers of migrating TNCC in the intersomitic pathway suggest interesting evolutionary differences. Together, our present results of the Egyptian cobra in combination with those on a colubrid and turtle supports intersomitic TNCC as a unique reptile phenomena.

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LncRNA MONC suppresses the malignant phenotype of Endometrial Cancer Stem Cells and Endometrial Carcinoma Cells by regulating the MiR-636/GLCE axis

10.21203/rs.3.rs-153939/v1 ◽

2021 ◽

Author(s):

Yibing Li ◽

Jianing Huo ◽

Junjian He ◽

xiaoxin Ma

Keyword(s):

Stem Cells ◽

Endometrial Cancer ◽

Cancer Stem Cells ◽

Endometrial Carcinoma ◽

Epithelial To Mesenchymal Transition ◽

Suppressive Effect ◽

Carcinoma Cells ◽

Biological Behavior ◽

Mesenchymal Transition ◽

Tumor Suppressive Effect

Abstract Background Emerging evidence shows that abnormal expression of long non-coding RNA is involved in the occurrence and development of various tumors. LncRNA MONC is abnormally expressed in head and neck squamous cell carcinoma, lung cancer, colorectal cancer, and acute megakaryocytic leukemia, but the biological function and potential regulatory mechanism of MONC in endometrial cancer stem cells (ECSCs) and endometrial cancer cells (ECCs) have not been studied. Methods We used qRT-PCR to detect the expression of MONC, miR-636 and GLCE in normal human endometrial tissues and endometrial carcinoma tissues. Luciferase assay was used to verify the binding sites between MONC and miR-636 and between miR-636 and GLCE. The double fluorescence in situ hybridization was used to locate MONC and miR-636 in cells. Endometrial cancer stem cells were obtained by Flow cytometry sorting assay. Sphere formation assay, CCK-8 assay, transwell invasion assay, cell cycle analysis and apoptosis assay were used to detect the effects of MONC/miR-636/GLCE axis on the malignant biological behavior of ECSCs and endometrial carcinoma cells (ECCs). The effect of MONC on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot. Finally, we conducted in vivo verification through Tumor xenografts in nude mice. Results In this study, we aimed to explore the tumor suppressive effect and mechanism of MONC in regulating ECSCs and ECCs. We found MONC is low expression in endometrial carcinoma (EC), MONC and miR-636 are relatively co-localized in the cytoplasm. MONC directly inhibits the malignant biological behavior of ECSCs and ECCs by directly inhibiting miR-636. Simultaneously, miR-636 may indirectly reduce the expression of MONC. Down-regulation of miR-636 may promote GLCE expression by targeting the 3'-untranslated region (UTR) of the downstream gene GLCE, thereby inhibiting the progression of ECSCs. MONC combined with miR-636 inhibited tumor epithelial-to-mesenchymal transition (EMT) process. In addition, we verified the tumor suppressive effect of MONC in nude mice, miR-636 can rescue the tumor suppressive effect of overexpressing MONC. Conclusions In conclusion, this study shows that MONC inhibits the malignant phenotypes of ECSCs and ECCs by regulating the miR-636/GLCE axis. The MONC/miR-636/GLCE axis may provide novel treatment avenues for human EC.

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DNA Methylation of TGFβ Target Genes: Epigenetic Control of TGFβ Functional Duality in Liver Cancer

Cells ◽

10.3390/cells10092207 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2207

Author(s):

Kevin Bévant ◽

Matthis Desoteux ◽

Abdel Hady A. Abdel Wahab ◽

Sabrin A. Abdel Wahab ◽

Ayman Mohamed Metwally ◽

...

Keyword(s):

Dna Methylation ◽

Tumor Progression ◽

Transforming Growth Factor Beta ◽

Epithelial To Mesenchymal Transition ◽

Target Genes ◽

Transforming Growth Factor ◽

Early Stage ◽

Potent Inducer ◽

Mesenchymal Transition ◽

Epigenetic Control

Transforming growth factor beta (TGFβ) plays a key role in liver carcinogenesis. However, its action is complex, since TGFβ exhibits tumor-suppressive or oncogenic properties, depending on the tumor stage. At an early stage TGFβ exhibits cytostatic features, but at a later stage it promotes cell growth and metastasis, as a potent inducer of epithelial to mesenchymal transition (EMT). Here, we evaluated DNA methylation as a possible molecular mechanism switching TGFβ activity toward tumor progression in hepatocellular carcinoma (HCC). We report that decitabine, a demethylating agent already used in the clinic for the treatment of several cancers, greatly impairs the transcriptional response of SNU449 HCC cells to TGFβ. Importantly, decitabine was shown to induce the expression of EMT-related transcription factors (e.g., SNAI1/2, ZEB1/2). We also report that the promoter of SNAI1 was hypomethylated in poor-prognosis human HCC, i.e., associated with high grade, high AFP level, metastasis and recurrence. Altogether, the data highlight an epigenetic control of several effectors of the TGFβ pathway in human HCC possibly involved in switching its action toward EMT and tumor progression. Thus, we conclude that epidrugs should be carefully evaluated for the treatment of HCC, as they may activate tumor promoting pathways.

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Complete Clinical Response in Stage IVB Endometrioid Endometrial Carcinoma after First-Line Pembrolizumab Therapy: Report of a Case with Isolated Loss of PMS2 Protein

Case Reports in Oncology ◽

10.1159/000510000 ◽

2020 ◽

Vol 13 (3) ◽

pp. 1067-1074

Author(s):

Jesus Paula Carvalho ◽

Auro Del Giglio ◽

Maria Isabel Achatz ◽

Filomena Marino Carvalho

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Endometrial Carcinoma ◽

Early Stage ◽

Gynecological Cancer ◽

Stage Iv ◽

Protein Loss ◽

First Line ◽

Early Stage Disease ◽

Endometrioid Endometrial Carcinoma

Endometrial cancer is the only gynecological cancer that is rising in incidence and associated mortality worldwide. Although most cases are diagnosed as early stage disease, with chances of cure after primary surgical treatment, those with advanced or metastatic disease have a poor prognosis because of the quality of treatment options that are currently available. Mismatch repair (MMR)-deficient cancers are susceptible to programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 inhibitors. The US Food and Drug Administration granted accelerated approval to pembrolizumab for MMR-deficient tumors, the first tumor-agnostic approval for a drug. We present a case of stage IV endometrioid endometrial carcinoma with isolated PMS2 protein loss, in which treatment with first-line pembrolizumab therapy achieved a complete clinical and pathological response of tumor.

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