Dataset Information

DNER promotes epithelial-mesenchymal transition and prevents chemosensitivity through the Wnt/?-catenin pathway in breast cancer.

ABSTRACT: Breast cancer (BC) is the most common malignant tumour in women worldwide, and one of the most common fatal tumours in women. Delta/Notch-like epidermal growth factor (EGF)-related receptor (DNER) is a transmembrane protein involved in the development of tumours. The role and potential mechanism of DNER in epithelial-mesenchymal transition (EMT) and apoptosis in BC are not fully understood. We find that DNER is overexpressed in BC tissue, especially triple-negative breast cancer (TNBC) tissue, and related to the survival of BC and TNBC patients. In addition, DNER regulates cell EMT to enhance the proliferation and metastasis of BC cells via the Wnt/?-catenin pathway in vitro and in vivo. Moreover, the expression levels of ?-catenin and DNER in BD tissue are positively correlated. The simultaneously high expression of DNER and ?-catenin contributes to poor prognosis in BC patients. Finally, DNER protects BC cells from epirubicin-induced growth inhibition and apoptosis via the Wnt/?-catenin pathway. In conclusion, these results suggest that DNER induces EMT and prevents apoptosis by the Wnt/?-catenin pathway, ultimately promoting the malignant progression of BC. In conclusion, our study demonstrates that DNER functions as an oncogene and potentially valuable therapeutic target for BC.

SUBMITTER: Wang Z

PROVIDER: S-EPMC7434780 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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DNER promotes epithelial-mesenchymal transition and prevents chemosensitivity through the Wnt/β-catenin pathway in breast cancer.

Wang Zhong Z Li Zhiyu Z Wu Qi Q Li Chenyuan C Li Juanjuan J Zhang Yimin Y Wang Changhua C Sun Si S Sun Shengrong S

Cell death & disease 20200818 8

Breast cancer (BC) is the most common malignant tumour in women worldwide, and one of the most common fatal tumours in women. Delta/Notch-like epidermal growth factor (EGF)-related receptor (DNER) is a transmembrane protein involved in the development of tumours. The role and potential mechanism of DNER in epithelial-mesenchymal transition (EMT) and apoptosis in BC are not fully understood. We find that DNER is overexpressed in BC tissue, especially triple-negative breast cancer (TNBC) tissue, a ...[more]

PMID: 32811806

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Project description:BackgroundCigarette smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer. Epithelial-mesenchymal transition (EMT) is an essential pathophysiological process in COPD and plays an important role in airway remodeling, fibrosis, and malignant transformation of COPD. Previous studies have indicated FERMT3 is downregulated and plays a tumor-suppressive role in lung cancer. However, the role of FERMT3 in COPD, including EMT, has not yet been investigated.MethodsThe present study aimed to explore the potential role of FERMT3 in COPD and its underlying molecular mechanisms. Three GEO datasets were utilized to analyse FERMT3 gene expression profiles in COPD. We then established EMT animal models and cell models through cigarette smoke (CS) or cigarette smoke extract (CSE) exposure to detect the expression of FERMT3 and EMT markers. RT-PCR, western blot, immunohistochemical, cell migration, and cell cycle were employed to investigate the potential regulatory effect of FERMT3 in CSE-induced EMT.ResultsBased on Gene Expression Omnibus (GEO) data set analysis, FERMT3 expression in bronchoalveolar lavage fluid was lower in COPD smokers than in non-smokers or smokers. Moreover, FERMT3 expression was significantly down-regulated in lung tissues of COPD GOLD 4 patients compared with the control group. Cigarette smoke exposure reduced the FERMT3 expression and induces EMT both in vivo and in vitro. The results showed that overexpression of FERMT3 could inhibit EMT induced by CSE in A549 cells. Furthermore, the CSE-induced cell migration and cell cycle progression were reversed by FERMT3 overexpression. Mechanistically, our study showed that overexpression of FERMT3 inhibited CSE-induced EMT through the Wnt/β-catenin signaling.ConclusionsIn summary, these data suggest FERMT3 regulates cigarette smoke-induced epithelial-mesenchymal transition through Wnt/β-catenin signaling. These findings indicated that FERMT3 was correlated with the development of COPD and may serve as a potential target for both COPD and lung cancer.

Project description:Osteosarcoma (OS) is a rare type of tumor and mostly occurs in children and adolescents. Approximately 10‑25% of patients with OS have lung metastases, and lung damage caused by lung metastasis is the main cause of mortality. Therefore, studying the growth and metastasis of OS is key in reducing OS mortality and improving prognosis. The expression of long non‑coding RNA (lncRNA) cancer susceptibility 15 (CASC15) in OS patients or OS cell lines were quantified by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The expression of vimentin, E‑cadherin, N‑cadherin, and cyclin D were detected by RT‑qPCR and western blotting. Mice were injected with OS cell lines via the tail vein to observe tumor formation in the lung. CCK‑8 and EdU assays were utilized to evaluate cell proliferation. Both Ttranswell assay and cell scratch test detected cell migration. The results revealed that lncRNA‑CASC15 was highly expressed in clinical samples and OS cells. In vitro verification experiments revealed that CASC15 promoted the growth of OS cells. Rescue experiments demonstrated that CASC15 affected the cell cycle by activating the Wnt/β‑catenin pathway, thereby promoting cell proliferation. Furthermore, the transfection dose test indicated that lentiviruses expressing various doses of CASC15‑overexpression (oe‑CASC15) altered the proliferation and migration status of OS cells. CASC15 promoted OS cell metastasis both in vivo and in vitro. The overexpression of CASC15 revealed that the occurrence of metastasis was also related to the Wnt/β‑catenin pathway. The western blotting results revealed that CASC15 could lead to β‑catenin entering the nucleus via the Wnt pathway to promote the epithelial‑mesenchymal transition (EMT) of OS cells. To sum up, CASC15 promoted the proliferation of OS cells in vitro and the growth of OS xenograft tumors in vivo. Moreover, CASC15 promoted the entry of β‑catenin into the nucleus, thus activating the Wnt pathway and subsequently promoting the EMT of OS cells.

Dataset Information

DNER promotes epithelial-mesenchymal transition and prevents chemosensitivity through the Wnt/?-catenin pathway in breast cancer.

Publications

DNER promotes epithelial-mesenchymal transition and prevents chemosensitivity through the Wnt/β-catenin pathway in breast cancer.

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