FZD2 regulates cell proliferation and invasion in tongue squamous cell carcinoma

Huang, Li; Lu, You‐Guang; Xie, Jing; Gan, Rui‐Huan; Ding, Lin‐Can; Su, Bogong; Zhao, Yong; Lin, Lisong; Zheng, Dali

doi:10.7150/ijbs.33881

Cited by 24 publications

(21 citation statements)

References 34 publications

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“…Each member of FZDs can activate WNT signaling pathway through interacting with different WNT proteins [3]. As previously reported, FZD2 is dysregulated in various cancer types, such as oral squamous cell carcinoma [4]{Asano, 2017 #3793}, gastric cancer [5], endometrial cancer [6], hepatocellular carcinoma [7] and tongue squamous cell carcinoma [8]. There is also a study reported that FZD2 suppresses tumor growth in salivary adenoid cystic carcinoma [9].…”

Section: Introductionmentioning

confidence: 82%

FZD2 Promotes TGF-β-induced Epithelial-to-Mesenchymal Transition in Breast Cancer via Activating Notch Signaling Pathway

Tuluhong

Chen

Wang

et al. 2020

Preprint

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Background: Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our study was to detect the functions of FZD2 and explore its mechanism in BC.Methods: The level of FZD2 was measured in BC tissues by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC) respectively. Cell Counting Kit-8 (CCK-8), colony formation assay, transwell assays, wound healing assay and flow cytometry analyses were conducted separately to test cell viability, invasion, migration, apoptosis and cell cycle distribution. Epithelial-mesenchymal transition (EMT) biomarkers were determined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo.Results: FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT in BC cells in a transforming growth factor (TGF)-β1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway.Conclusion: FZD2 facilitates BC progression and promotes TGF-β1-inudced EMT process through activating Notch signaling pathway.

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Section: Introductionmentioning

confidence: 82%

FZD2 Promotes TGF-β-induced Epithelial-to-Mesenchymal Transition in Breast Cancer via Activating Notch Signaling Pathway

Tuluhong

Chen

Wang

et al. 2020

Preprint

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“…FZDs are reported to be involved not only in embryogenesis and development but also in tumor development and progression [ 9 , 10 ]. FZD2 was over-expressed in hepatocellular carcinoma (HCC) and head and neck squamous cell carcinoma compared to paracancerous tissues and significantly associated with the survival of patients [ 11 ]. In endometrial cancer, FZD2 could modulate the EMT process by activating Wnt signaling pathway [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Expression and prognostic impact of FZDs in pancreatic adenocarcinoma

Liu

Zhang

2021

BMC Gastroenterol

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Background Despite the high number of researches on pancreatic adenocarcinoma (PAAD) over past decades, little progress had been made due to lack of effective treatment regimens. We aimed to investigate the expression level, mutation, and clinical significance of the Frizzled (FZD) family in PAAD so as to establish a sufficient scientific evidence for clinical decisions and risk management. Methods PAAD samples were extracted from The Cancer Genome Atlas (TCGA). Oncomine, Gene expression profiling interactive analysis (GEPIA), human protein atlas (HPA), Kaplan–Meier Plotter, cBioPortal, LinkedOmics, DAVID database, and R software (× 64 3.6.2) were used to comprehensively analyze the roles of FZDs. p value below to 0.05 was considered as significant difference. Results In total, 179 PAAD tissues and 171 paracancerous tissues were included. The expression levels of FZD1, 2, 6, 7, and 8 were higher in PAAD tissues than those in normal pancreatic tissue. The higher the expression levels of FZD2 and FZD7, the higher the clinical stage. The overall survival (OS) time was significantly different between low FZD3, 4, 5, 6, and 9 expression group and high expression group. Multivariable analysis showed that FZD3 and FZD6 were independent prognostic factors. The recurrence free survival (RFS) time was significantly different between low FZD4 and FZD8 expression group and high expression group. The RFS difference between low FZD6 expression group and high expression group had not reached statistical significance (p = 0.067), which might be due to the small sample size. However, multivariable analysis showed that FZD6 was the only independent factor for RFS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that FZDs played a critical role in the Wnt signaling pathway, which was further confirmation that FZDs were transmembrane receptors of Wnt signaling pathway. Conclusions Our results strongly indicated a crucial role of the FZD family in PAAD. FZD3 and FZD6 could be potential prognostic and predictive markers, and FZD6 might also function as a potential therapeutic target in PAAD by blocking Wnt/β-catenin pathway.

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“…In addition, FZD2 is up-regulated in many types of cancers, which is considered to be a new predictor of tumor recurrence. It is involved in the metastasis of various cancers including endometrial cancer (14), neuroblastoma (15), oral squamous cell carcinoma (16), tongue squamous cell carcinoma (17), hepatocellular carcinoma (18), colon cancer (19), and prostate cancer (20,21). Recently, the down-regulation of miR-30a-3p/5p was reported to promote ESCC cell proliferation through the up-regulation of WNT2 and FZD2, respectively (7).…”

Section: Introductionmentioning

confidence: 99%

WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling

Zheng

Mao

et al. 2020

Front. Oncol.

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Esophageal cancer micro environment factor WNT2 was critical in cancer metastasis. However, very little is known about WNT2 receptors and their role in the malignant progression of ESCC. The clinical significance and underlying molecular mechanisms of FZD2, one of the receptors of WNT2, was further investigated in ESCC. We found that FZD2 expression was positively correlated with WNT2 levels in clinical ESCC specimens through database analysis. Upregulated FZD2 expression was detected in 69% (69/100) of the primary ESCC cases examined, and increased FZD2 expression was significantly correlated with poor prognosis (P < 0.05). Mechanistically, FZD2 induced the migration and invasion of ESCC cells by regulating the FZD2/STAT3 signaling. In vivo xenograft experiments further revealed the metastasis-promoting role of FZD2 in ESCC. Moreover, we found that the WNT2 ligand could stabilize and phosphorylate the FZD2 receptor by attenuating FZD2 ubiquitination, leading to the activation of STAT3 signaling and the initiation of ESCC cell metastasis. Collectively, our data revealed that a novel non-canonical WNT2/FZD2/STAT3 signaling axis is critical for ESCC progression. Strategies targeting this specific signaling axis might be developed to treat patients with ESCC.

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FZD2 regulates cell proliferation and invasion in tongue squamous cell carcinoma

Cited by 24 publications

References 34 publications

FZD2 Promotes TGF-β-induced Epithelial-to-Mesenchymal Transition in Breast Cancer via Activating Notch Signaling Pathway

FZD2 Promotes TGF-β-induced Epithelial-to-Mesenchymal Transition in Breast Cancer via Activating Notch Signaling Pathway

Expression and prognostic impact of FZDs in pancreatic adenocarcinoma

WNT2-Mediated FZD2 Stabilization Regulates Esophageal Cancer Metastasis via STAT3 Signaling

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