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

Abouhashem, Nehal S.; Ibrahim, Doaa; Mohamed, Abdel Motaleb

doi:10.1016/j.anndiagpath.2016.01.004

Cited by 22 publications

(18 citation statements)

References 30 publications

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“…Reduced CDH1 expression in a wide range of tumor types, including EC, has been associated with variety of negative prognostic features and poor outcomes. [44][45][46][47][48][49] Tumor tissue sections were not available to evaluate the primary tumors with FOXA2 mutations for changes in CDH1 protein levels or evidence of EMT. Nonetheless, our data on CDH1 expression in vitro and in vivo are consistent with loss of FOXA2 transcriptional activity associated with EC mutations.…”

Section: Discussionmentioning

confidence: 99%

Functional characterization of recurrent FOXA2 mutations seen in endometrial cancers

Neff

Rush

Smith

et al. 2018

Intl Journal of Cancer

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FOXA2, a member of the forkhead family of DNA-binding proteins, is frequently mutated in uterine cancers. Most of the mutations observed in uterine cancers are frameshifts and stops. FOXA2 is considered to be a driver gene in uterine cancers, functioning as a haploinsufficient tumor suppressor. The functional consequences of FOXA2 mutations, however, have not yet been determined. We evaluated the effects that frameshift mutations and a recurrent missense mutation have on FOXA2 transcriptional activity. Recurrent N-terminal frameshifts resulted in truncated proteins that failed to translocate to the nucleus and have no transcriptional activity using an E-cadherin/luciferase reporter assay. Protein abundance was reduced for the recurrent p.S169 W mutation, as was transcriptional activity. A C-terminal frameshift mutation had increased FOXA2 levels evidenced by both Western blot and immunofluorescence. Given that FOXA2 is a recognized activator of E-cadherin (CDH1) expression and E-cadherin's potential role in epithelial-to-mesenchymal transition in a wide range of cancer types, we tested the hypothesis that FOXA2 mutations in primary uterine cancer specimens would be associated with reduced CDH1 transcript levels. qRT-PCR revealed significantly lower levels of CDH1 expression in primary tumors with FOXA2 mutations. Our findings in vitro and in vivo suggest that reduced transcriptional activity associated with FOXA2 mutations in uterine cancers is likely to contribute to protumorigenic changes in gene expression.

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Section: Discussionmentioning

confidence: 99%

Functional characterization of recurrent FOXA2 mutations seen in endometrial cancers

Neff

Rush

Smith

et al. 2018

Intl Journal of Cancer

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“…Although varying in detail, most studies are consistent that low E-cadherin expression correlates with increasing aggressiveness, poor differentiation, and deep myometrial invasion of the carcinoma [130,131,132,133,134,135,136,137,138,139]. In accordance, E-cadherin was found to be more often and prominently expressed in endometrioid adenocarcinoma than in serous papillary or clear cell tumors [131,139,140], and a high E-cadherin level has been associated with reduced mortality, disease progression, and disease recurrence rate and thus is associated with a better prognosis [141].…”

Section: Direct Cell–cell Interactions In Endometrial Pathophysiologymentioning

confidence: 99%

“…Further insights on the role of E-cadherin in endometrioid adenocarcinoma are constantly emerging. For example, in endometrioid endometrial carcinoma the expression of the E-cadherin suppressor Snail was found to be negatively correlated with E-cadherin expression [130] and was correlated with abnormal E-cadherin expression in metastases of this tumor [132]. …”

Section: Direct Cell–cell Interactions In Endometrial Pathophysiologymentioning

confidence: 99%

Direct Cell–Cell Interactions in the Endometrium and in Endometrial Pathophysiology

Grund

Grümmer

2018

IJMS

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Cell contacts exhibit a considerable influence on tissue physiology and homeostasis by controlling paracellular and intercellular transport processes, as well as by affecting signaling pathways. Since they maintain cell polarity, they play an important role in cell plasticity. The knowledge about the junctional protein families and their interactions has increased considerably during recent years. In contrast to most other tissues, the endometrium undergoes extensive physiological changes and reveals an extraordinary plasticity due to its crucial role in the establishment and maintenance of pregnancy. These complex changes are accompanied by changes in direct cell–cell contacts to meet the various requirements in the respective developmental stage. Impairment of this sophisticated differentiation process may lead to failure of implantation and embryo development and may be involved in the pathogenesis of endometrial diseases. In this article, we focus on the knowledge about the distribution and regulation of the different junctional proteins in the endometrium during cycling and pregnancy, as well as in pathologic conditions such as endometriosis and cancer. Decoding these sophisticated interactions should improve our understanding of endometrial physiology as well as of the mechanisms involved in pathological conditions.

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“…Additionally, dietary cholesterol consumption, including saturated fatty acid, unsaturated fatty acid, and cholesterol intake, in uences EC risk by regulating the production, metabolism, and excretion of endogenous hormones (6). Secondly, Epithelial-to-Mesenchymal Transition (EMT) is an important step towards the invasion and metastasis of cancer (19). Hsu et al demonstrated that epithelial cell adhesion molecule (EpCAM)-regulated transcription exerted in uences on nanomechanical properties of EC cells, which promotes EMT (20).…”

Section: Discussionmentioning

confidence: 99%

“…GO terms with Pvalue < 0.05 were selected and ranked by enrichment score (-log10 (P-value)). Among the BP terms, response to cholesterol, epithelial to mesenchymal transition, and base-excision repair have been reported to be associated with tumor (6,(18)(19)(20)(21). In MF terms, WNT-activated receptor activity and WNT-protein binding might play a role in tumors.…”

Section: Go and Kegg Pathway Analysesmentioning

confidence: 99%

Characteristics of Circular RNA Expression in Ishikawa Human Endometrial Carcinoma Cells with Progesterone Treatment

Wang¹,

Zheng²,

Cao³

et al. 2020

Preprint

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Background Progestins are commonly used as the conservative endocrine treatment of young early endometrial cancer (EC) patients. Circular RNAs (circRNAs) are new group players in multiple cellular functions. This study aims to identify the differentially expressed circular RNAs (DE-circRNAs) in endometrial cancer (EC) cells upon the progesterone treatment, aiding in the understanding of the impact of circRNAs in progestin therapy. Methods RNA-seq analysis was used to identify the DE-circRNAs between MPA-treated and -non-treated Ishikawa cell lines. Functional enrichment analysis and circRNA-miRNA interaction network analysis were applied to these DE-circRNAs, validated by qRT-PCR analyses. Moreover, shRNA knockdown was utilized to explore the circRNA function. Results A total of 87 circRNAs were differentially expressed in Ishikawa cell lines with MPA treatment compared with that of control cells (|fold change| ≥2.0, p < 0.05). Besides, these circRNAs were mainly enriched in cancer-related pathways, including response to cholesterol, epithelial to mesenchymal transition, and base-excision repair. The competing endogenous RNA (ceRNA) network showed that miR-296-3p, miR-1236-3p, and miR-144-5p were related to cancer. Furthermore, the qPCR results were coincident with the RNA-seq data. Of note, hsa_circ_0001860 was significantly induced upon MPA treatment. Knockdown of hsa_circ_0001860 can partially rescue the MPA-inhibited cell proliferation and invasion and regulate the expression of its interacting miRNAs. Conclusions This is the first time to evaluate the circRNA expression profile in progesterone treatment for EC. These circRNAs (e.g., hsa_circ_0001860) may be used as potential diagnostic biomarkers and treatment targets for the evaluation of EC progesterone treatment.

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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

Cited by 22 publications

References 30 publications

Functional characterization of recurrent FOXA2 mutations seen in endometrial cancers

Functional characterization of recurrent FOXA2 mutations seen in endometrial cancers

Direct Cell–Cell Interactions in the Endometrium and in Endometrial Pathophysiology

Characteristics of Circular RNA Expression in Ishikawa Human Endometrial Carcinoma Cells with Progesterone Treatment

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