<scp>LGR</scp>5 promotes epithelial ovarian cancer proliferation, metastasis, and epithelial–mesenchymal transition through the Notch1 signaling pathway

Liu, Wenxue; Zhang, Jing; Gan, Xu-Pei; Shen, Fei; Yang, Xiaoming; Du, Na; Xia, Dandan; Liu, Lei; Qiao, Lianqiao; Pan, Jufang; Sun, Yunyan; Xi, Xiaowei

doi:10.1002/cam4.1485

Cited by 23 publications

(19 citation statements)

References 33 publications

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“…We demonstrated that OPN3 could promote the EMT and tumor metastasis in LUAD. It has been previously reported that a variety of G‐protein coupled‐receptor proteins promote metastasis by affecting the EMT process of cancer cells, including in lung cancer . However, more studies are warranted to further explore the molecular mechanism of OPN3 in affecting the EMT of LUAD.…”

Section: Discussionmentioning

confidence: 99%

Expression of OPN3 in lung adenocarcinoma promotes epithelial‐mesenchymal transition and tumor metastasis

Wang

Yang

et al. 2019

Thoracic Cancer

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Background: Lung adenocarcinoma is the most common pathological lung cancer and an important cause of cancer-related death. Metastasis is a major underlying reason for poor prognosis of lung adenocarcinoma. Opsin3 (OPN3), a member of the guanine nucleotide-binding protein-coupled receptor superfamily, has been identified to affect the apoptosis of hepatoma cells by modulating the phosphorylation of Akt and Bcl2/Bax. However, the expression and role of OPN3 in lung adenocarcinoma remains unclear. Methods: Opsin3 expression in lung adenocarcinoma tissues was detected by western blot, qPCR, and immunohistochemistry. Changes in cell migration and invasion ability resulting from the change of OPN3 expression level were detected by wound healing and transwell migration assays. Changes in the markers of epithelial-mesenchymal transformation were detected by western blot and qPCR. Results: Opsin3 expression in lung adenocarcinoma tissues was higher than that in normal lung tissues. Patients with high expression of OPN3 had lower survival rates. Owing to overexpression of OPN3, the HCC827 cells showed enhanced invasion and migration ability in vitro. Upon decreasing the expression of OPN3, the invasion and migration ability of the A549 cells decreased. Conclusion: Our study demonstrated for the first time that OPN3 gene enhanced the metastasis in lung adenocarcinoma, and its overexpression promoted epithelial-mesenchymal transition. Key points: A significant finding of the study was that OPN3 acted an oncogene in promoting lung adenocarcinoma metastasis. Our study complemented the research on the expression and function of OPN3 in lung adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Expression of OPN3 in lung adenocarcinoma promotes epithelial‐mesenchymal transition and tumor metastasis

Wang

Yang

et al. 2019

Thoracic Cancer

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“…Altered membrane potentials are known to induce cellular proliferation, migration, and apoptosis [ 31 ]. LGR5 is a member of glycoprotein hormone receptor sub-family, which has been demonstrated to regulate tumorigenesis and metastasis in EOC through Notch1 signaling [ 32 ]. The notch pathway is known to regulate the self-renewal and survival of CSCs.…”

Section: Discussionmentioning

confidence: 99%

“…CXCR4 is a critical molecule in cisplatin treatment for EOC patients and its inhibition can be a potential strategy to address chemoresistance [ 72 ]. LGR5 promotes ovarian cell proliferation, progression, and EMT [ 32 ] and is associated with chemoresistance in cervical cancer [ 34 ]. In bladder cancer, PAX5/PTGS2 cascade is known to induce cisplatin resistance [ 73 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis and verification of molecular targets in ovarian cancer stem-like cells

Behera

Ashraf

Srivastava

et al. 2020

Heliyon

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Background Epithelial ovarian cancer (EOC) is a lethal and aggressive gynecological malignancy. Despite recent advances, existing therapies are challenged by a high relapse rate, eventually resulting in disease recurrence and chemoresistance. Emerging evidence indicates that a subpopulation of cells known as cancer stem-like cells (CSLCs) exists with non-tumorigenic cancer cells (non-CSCs) within a bulk tumor and is thought to be responsible for tumor recurrence and drug-resistance. Therefore, identifying the molecular drivers for cancer stem cells (CSCs) is critical for the development of novel therapeutic strategies for the treatment of EOC. Methods Two gene datasets were downloaded from the Gene Expression Omnibus (GEO) database based on our search criteria. Differentially expressed genes (DEGs) in both datasets were obtained by the GEO2R web tool. Based on log 2 (fold change) >2, the top thirteen up-regulated genes and log 2 (fold change) < -1.5 top thirteen down-regulated genes were selected, and the association between their expressions and overall survival was analyzed by OncoLnc web tool. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathways analysis, and protein-protein interaction (PPI) networks were performed for all the common DEGs found in both datasets. SK-OV-3 cells were cultured in an adherent culture medium and spheroids were generated in suspension culture with CSCs specific medium. RNA from both cell population was extracted to validate the selected DEGs expression by q-PCR. Growth inhibition assay was performed in SK-OV-3 cells after carboplatin treatment. Results A total of 200 DEGs, 117 up-regulated and 83 down-regulated genes were commonly identified in both datasets. Analysis of pathways and enrichment tests indicated that the extracellular matrix part, cell proliferation, tissue development, and molecular function regulation were enriched in CSCs. Biological pathways such as interferon-alpha/beta signaling, molecules associated with elastic fibers, and synthesis of bile acids and bile salts were significantly enriched in CSCs. Among the top 13 up-regulated and down-regulated genes, MMP1 and PPFIBP1 expression were associated with overall survival. Higher expression of ADM, CXCR4, LGR5, and PTGS2 in carboplatin treated SK-OV-3 cells indicate a potential role in drug resistance. Conclusions The molecular signature and signaling pathways enriched in ovarian CSCs were identified by bioinformatics analysis. This analysis could provide further research ideas to find the new mechanism and novel potential therapeutic targets for ovarian CSCs.

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“…Other works have supported this idea since LGR5 + seems to be related to progression of different cancers, such as colon [24], papillary thyroid [25], breast [26], and ovarian cancers [27] by promoting epithelial ovarian cancer proliferation, metastasis, and epithelial–mesenchymal transition (EMT). Furthermore, LGR5 is overexpressed in ovarian cancer tissue compared to normal tissue [28]. Moreover, it is well known that patients with endometriosis have a higher risk of developing ovarian cancer [29].…”

Section: Discussionmentioning

confidence: 99%

Lgr5 Does Not Vary Throughout the Menstrual Cycle in Endometriotic Human Eutopic Endometrium

Vallvé-Juanico

Barón

Suárez-Salvador

et al. 2018

IJMS

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Endometriosis is characterized by the abnormal presence of endometrium outside of the uterus, resulting in pelvic pain and infertility. The leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) has been postulated to be a marker of stem cells in the endometrium. However, LGR5+ cells have a macrophage-like phenotype in this tissue, so it is unclear what role LGR5+ cells actually play in the endometrium. Macrophages serve an important function in the endometrium to maintain fertility, while LGR5+ cells generally have a role in tumor progression and are involved in invasion in some cancers. We sought to determine whether LGR5+ cells vary across the menstrual cycle in women with endometriosis and whether there are implications for LGR5 in the aggressiveness of endometriosis and reproductive outcomes. We performed immunofluorescence, flow cytometry, and primary culture in vitro experiments on eutopic and ectopic endometrium from healthy and endometriosis patients and observed that neither LGR5+ cells nor LGR5 expression varied throughout the cycle. Interestingly, we observed that LGR5+ cell percentage overexpressing CD163 (anti-inflammatory marker) was higher in healthy endometrium, suggesting that in endometriosis, endometrium presents a more pro-inflammatory phenotype that likely leads to poor obstetric outcomes. We also observed higher levels of LGR5+ cells in ectopic lesions compared to eutopic endometrium and specifically in deep infiltrating endometriosis, indicating that LGR5 could be involved in progression and aggressiveness of the disease.

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LGR5 promotes epithelial ovarian cancer proliferation, metastasis, and epithelial–mesenchymal transition through the Notch1 signaling pathway

Cited by 23 publications

References 33 publications

Expression of OPN3 in lung adenocarcinoma promotes epithelial‐mesenchymal transition and tumor metastasis

Expression of OPN3 in lung adenocarcinoma promotes epithelial‐mesenchymal transition and tumor metastasis

Bioinformatics analysis and verification of molecular targets in ovarian cancer stem-like cells

Lgr5 Does Not Vary Throughout the Menstrual Cycle in Endometriotic Human Eutopic Endometrium

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