Dataset Information

Frizzled7 Promotes Epithelial-to-mesenchymal Transition and Stemness Via Activating Canonical Wnt/?-catenin Pathway in Gastric Cancer.

ABSTRACT: Aberrant activation of Wnt signaling is a crucial event in tumor development and metastasis. Wnt signaling is commonly divided into canonical and non-canonical signaling pathways based on whether ?-catenin is activated (canonical). The two signaling pathways are initiated by Wnt ligand binding to the surface Frizzled (FZD) receptors, and regulate cancer stem cell self-renewal and epithelial-mesenchymal transition (EMT). Frizzled 7 (FZD7), a member of Frizzled family, promotes cell proliferation and invasiveness in many cancers, suggesting that FZD7 transmitting Wnt signaling is important for driving cancer growth. FZD7 expression has been reported to be up-regulated in human primary gastric cancer tissues. However, the molecular mechanism by which FZD7 promotes gastric cancer(GC) development and progression is not fully understood. Our present study showed that FZD7 was overexpressed in clinical GC samples, and thus was correlated with tumor invasion, lymphatic and organ metastasis, late TNM stages and poor patient survival. The endogenous expression of FZD7 was significantly increased in cancer stem cell-enriched spheres compared with adherent cells. Furthermore, RNA interference-mediated silencing of FZD7 inhibited proliferation, migration and invasion in gastric cancer cells. Moreover, ablation of FZD7 down-regulated EMT and the expression levels of cancer stem cell markers, and these inhibitions were associated with attenuated canonical Wnt/?-catenin signaling. The results suggest that Wnt canonical pathway may contribute to tumorigenesis and metastasis, indicating that FZD7 could be a potential therapeutic target for gastric cancer.

SUBMITTER: Li G

PROVIDER: S-EPMC5859474 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Frizzled7 Promotes Epithelial-to-mesenchymal Transition and Stemness Via Activating Canonical Wnt/β-catenin Pathway in Gastric Cancer.

Li Guanman G Su Qiao Q Liu Haibo H Wang Dong D Zhang Wenhui W Lu Zhenhai Z Chen Yu Y Huang Xiaohui X Li Wen W Zhang Changhua C He Yulong Y Fu Li L Bi Jiong J

International journal of biological sciences 20180212 3

Aberrant activation of Wnt signaling is a crucial event in tumor development and metastasis. Wnt signaling is commonly divided into canonical and non-canonical signaling pathways based on whether β-catenin is activated (canonical). The two signaling pathways are initiated by Wnt ligand binding to the surface Frizzled (FZD) receptors, and regulate cancer stem cell self-renewal and epithelial-mesenchymal transition (EMT). Frizzled 7 (FZD7), a member of Frizzled family, promotes cell proliferation ...[more]

PMID: 29559846

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Project description:Cancer pain is a common and severe complication of human breast cancer, and relieving pain is fundamental strategy in the treatment. Fentanyl, as an opioid analgesic, is widely used in breast cancer patients. However, little is known about its effects on stemness and epithelial-mesenchymal transition (EMT) of breast cancer cells. Aberrant protein glycosylation is involved in cancer malignancy. The α1, 6-fucosylation is an important type of glycosylation, and the elevated α1, 6-fucosylation catalyzed by fucosyltransferase VIII (FUT8) is found in many tumors. However, whether 1, 6-fucosylation is involved in regulating stemness and EMT, and stimulated by fentanyl is not clear. In this study, we found that fentanyl induced stemness and EMT in MCF-7 and MDA-MB-231 breast cancer cells by analysis of sphere formation, expression of stemness markers (Sox2, Oct4) and EMT markers (N-cadherin, E-cadherin and Vimentin). Results also showed that fentanyl upregulated FUT8 gene and protein expression by qPCR, Western blot and immunofluorescent staining, as well as α1, 6-fucosylation level by Lectin blot and Lectin fluorescent staining. Furthermore, decreased or blocked α1, 6-fucosylation by FUT8 siRNA transfection or LCA Lectin blockage reduced stemness and EMT. Additionally, fentanyl activated the key molecules and target genes in Wnt/β-catenin signaling pathway. LGK-974 (an inhibitor of Wnt ligands) suppressed fentanyl-mediated upregulation of α1, 6-fucosylation, stemness and EMT. The results of tumor xenograft demonstrated that fentanyl enhanced tumor growth, α1, 6-fucosylation, stemness and EMT. Taken together, our study reveals that fentanyl upregulated FUT8 expression, which increased α1, 6-fucosylation level through activation of Wnt/β-catenin signaling pathway, thereby, induce stemness and EMT of breast cancer cells. This study suggest a potential side effect of fentanyl in the treatment of cancer, which may guide the safety of fentanyl in the clinical application.

Dataset Information

Frizzled7 Promotes Epithelial-to-mesenchymal Transition and Stemness Via Activating Canonical Wnt/?-catenin Pathway in Gastric Cancer.

Publications

Frizzled7 Promotes Epithelial-to-mesenchymal Transition and Stemness Via Activating Canonical Wnt/β-catenin Pathway in Gastric Cancer.

Similar Datasets

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