Dataset Information

Quercetin Suppresses Human Glioblastoma Migration and Invasion via GSK3β/β-catenin/ZEB1 Signaling Pathway.

ABSTRACT: High invasiveness is a biological and clinical characteristic of glioblastoma and predicts poor prognosis of patients. Quercetin, a natural flavonoid compound, exhibits anticancer activity. However, we have a limited understanding of the possible underlying mechanism of quercetin in glioblastoma. In this study, we investigated the anticancer effect of quercetin in human glioblastoma cells. Our results showed that quercetin markedly suppressed the viability of glioblastoma cells in vitro and in vivo, and significantly inhibited glioblastoma cell migration and invasion. Moreover, quercetin reversed EMT-like mesenchymal phenotype and reduced the expression levels of EMT-related markers. Furthermore, we found that quercetin suppressed GSK-3β/β-catenin/ZEB1 signaling in glioblastoma. Taken together, our results demonstrate that quercetin inhibited migration and invasion of human glioma cells by suppressing GSK3β/β-catenin/ZEB1 signaling. Our study provides evidence that quercetin is a promising therapeutic natural compound to treat glioblastoma.

SUBMITTER: Chen B

PROVIDER: S-EPMC9663482 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Quercetin Suppresses Human Glioblastoma Migration and Invasion via GSK3β/β-catenin/ZEB1 Signaling Pathway.

Chen Bo B Li Xiaoli X Wu Lihong L Zhou Duanfang D Song Yi Y Zhang Limei L Wu Qiuya Q He Qichen Q Wang Gang G Liu Xu X Hu Hui H Zhou Weiying W

Frontiers in pharmacology 20221101

High invasiveness is a biological and clinical characteristic of glioblastoma and predicts poor prognosis of patients. Quercetin, a natural flavonoid compound, exhibits anticancer activity. However, we have a limited understanding of the possible underlying mechanism of quercetin in glioblastoma. In this study, we investigated the anticancer effect of quercetin in human glioblastoma cells. Our results showed that quercetin markedly suppressed the viability of glioblastoma cells <i>in vitro</i> a ...[more]

PMID: 36386155

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Project description:BackgroundPancreatic cancer is one of the most lethal disease with highly fatal and aggressive properties. Lymph node ratio (LNR), the ratio of the number of metastatic lymph nodes to the total number of examined lymph nodes, is an important index to assess lymphatic metastasis and predict prognosis, but the molecular mechanism underlying high LNR was unclear.MethodsGene expression and clinical information data of pancreatic cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Patients in TCGA were averagely divided into low and high LNR groups. Then, Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to build co-expression network to explore LNR-related modules and hub genes. GO and KEGG analysis was performed to find key pathways related to lymph node metastasis. Next, GSE101448 and the overall survival data in TCGA was employed to further select significant genes from hub genes. Considering the key role of CHRNB2 in LNR and survival, gene set enrichment analysis (GSEA) was applied to find pathways related to CHRNB2 expression in pancreatic cancer. The contribution of CHRNB2 to migrative and invasive ability of pancreatic cancer cells was confirmed by Transwell assays. We finally explored the role of CHRNB2 in EMT and β-catenin pathway via Western Blot.ResultsHigh LNR was significantly related to high T stages and poor prognosis. In WGCNA, 14 hub genes (COL5A1, FN1, THBS2, etc.) were positively related to high LNR, 104 hub genes (FFAR1, SCG5, TMEM63C, etc.) were negatively related to high LNR. After taking the intersection with GSE101448, 13 genes (CDK5R2, SYT7, CACNA2D2, etc.) which might prevent lymph node metastasis were further selected. Among them, CHRNB2 showed the strongest relationship with long survival. Moreover, CHRNB2 also negatively related to the T stages and LNR. Next, knockdown of CHRNB2 expression could acetylcholine (ACh)-independently increase the migration and invasion of pancreatic cancer cells, while CHRNB2 overexpression ACh-independently decrease the migration and invasion of pancreatic cancer cells. For exploring the underlying mechanism, CHRNB2 downregulated β-catenin pathway might through controlling its upstream regulators such as SOX6, SRY, SOX17, and TCF7L2.ConclusionsCHRNB2 negatively relates to lymph node metastasis in pancreatic cancer patients. CHRNB2 could inhibit β-catenin pathway, EMT, migration and invasion of pancreatic cancer cells via ACh-independent mechanism.

Dataset Information

Quercetin Suppresses Human Glioblastoma Migration and Invasion via GSK3β/β-catenin/ZEB1 Signaling Pathway.

Publications

Quercetin Suppresses Human Glioblastoma Migration and Invasion via GSK3β/β-catenin/ZEB1 Signaling Pathway.

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