Frizzled2 mediates the migration and invasion of human oral squamous cell carcinoma cells through the regulation of the signal transducer and activator of transcription-3 signaling pathway

Zhang, Enjiao; Li, Zhenning; Xu, Zhongfei; Duan, Weiyi; Sun, Changfu; Lu, Li

doi:10.3892/or.2015.4285

Cited by 20 publications

(20 citation statements)

References 35 publications

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“…Exposing EC cells to β-catenin stabilization antagonist XAV939 did affect Fzd2-mediated cell migration, further suggesting the dependence on the canonical Wnt pathway. However, previous studies have shown that Wnt5-Fzd2 activates both β-catenin-dependent (canonical) and β-catenin-independent (noncanonical) signaling (25)(26)(27). Moreover, at some stage of tumor progression, a switch appears to arise between β-catenin-dependent and β-catenin-independent signaling, consistent with the finding that XAV939 could not fully reverse the Fzd2-mediated cell migration.…”

Section: Discussionsupporting

confidence: 85%

Promotion of epithelial-mesenchymal transition by Frizzled2 is involved in the metastasis of endometrial cancer

et al. 2016

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The Wnt signaling pathway is essential for embryonic development, and genetic alteration in this network is closely correlated with tumorigenesis and progression. Previous research has shown that Wnt receptor Frizzled2 (Fzd2) is elevated in many metastatic cancer cell lines and high grade tumors. Yet, little is known about the Fzd2 expression and activity in human endometrial cancer (EC). In this study, we present evidence of a direct role of Fzd2 in human EC. We found that Fzd2 expression was higher in EC than that in adjacent normal tissues, and was correlated with epithelial‑mesenchymal transition markers. Next, it was determined that the stable overexpression of Fzd2 in HEC-1B and Ishikawa cells promoted cell migration and induced an EMT phenotype. Conversely, RNA interference-mediated depletion of Fzd2 inhibited EC cell migration. Additionally, mechanistic investigation revealed that elevated Fzd2 expression activated canonical Wnt signaling and was blocked by canonical Wnt signaling inhibitor XAV939. However, Fzd2 did not influence the proliferation of EC cells. Thus, Fzd2 may be a potential marker for EC metastasis and a target for future therapies for this disease.

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Section: Discussionsupporting

confidence: 85%

Promotion of epithelial-mesenchymal transition by Frizzled2 is involved in the metastasis of endometrial cancer

et al. 2016

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“…These receptors orchestrate growth and migration of HNSCC in response to diverse autocrine or paracrine signal ligands in tumors (19,23,35). We also identified other cell signaling receptors such as ITGA6, SERPINE1, and FZD2, which have been implicated in proliferation, adhesion, migration, and differentiation of HNSCC both in vitro and in vivo (17,24,36,37).…”

Section: Discussionmentioning

confidence: 84%

Integrated Genomic and Functional microRNA Analysis Identifies miR-30-5p as a Tumor Suppressor and Potential Therapeutic Nanomedicine in Head and Neck Cancer

Saleh

Cheng

Martin

et al. 2019

Clinical Cancer Research

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Purpose: To identify deregulated and inhibitory miRNAs and generate novel mimics for replacement nanomedicine for head and neck squamous cell carcinomas (HNSCC). Experimental Design: We integrated miRNA and mRNA expression, copy number variation, and DNA methylation results from The Cancer Genome Atlas (TCGA), with a functional genome-wide screen. Results: We reveal that the miR-30 family is commonly repressed, and all 5 members sharing these seed sequence similarly inhibit HNSCC proliferation in vitro. We uncover a previously unrecognized inverse relationship with overexpression of a network of important predicted target mRNAs deregulated in HNSCC, that includes key molecules involved in proliferation (EGFR, MET, IGF1R, IRS1, E2F7), differentiation (WNT7B, FZD2), adhesion, and invasion (ITGA6, SER-PINE1). Reexpression of the most differentially repressed family member, miR-30a-5p, suppressed this mRNA program , selected signaling proteins and pathways, and inhibited cell proliferation, migration, and invasion in vitro. Furthermore, a novel miR-30a-5p mimic formulated into a targeted nanomedicine significantly inhibited HNSCC xenograft tumor growth and target growth receptors EGFR and MET in vivo. Significantly decreased miR-30a/e family expression was related to DNA promoter hypermethylation and/or copy loss in TCGA data, and clinically with decreased diseasespecific survival in a validation dataset. Strikingly, decreased miR-30e-5p distinguished oropharyngeal HNSCC with poor prognosis in TCGA (P ¼ 0.002) and validation (P ¼ 0.007) datasets, identifying a novel candidate biomarker and target for this HNSCC subset. Conclusions: We identify the miR-30 family as an important regulator of signal networks and tumor suppressor in a subset of HNSCC patients, which may benefit from miRNA replacement nanomedicine therapy.

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“…They concluded that Fzd2 mediates the migration and invasion of OSCC cells at least partly by regulating the STAT3 signaling pathway. They suggest that Fzd2 could be a novel therapeutic target of OSCC …”

Section: Discussionmentioning

confidence: 99%

“…They suggest that Fzd2 could be a novel therapeutic target of OSCC. 23 Frizzled2 (Fzd2) is a receptor for wingless-type MMTV integration site family members (Wnts), the aberrant overexpression of which has been noted to contribute to cancer metastasis. Wnt5a-Fzd2 pathway may be involved in OSCC metastasis.…”

Section: Discussionmentioning

confidence: 99%

Pathway based prognostic gene expression profile of buccal and gingivo‐buccal oral squamous cell carcinoma in smokeless tobacco chewers

et al. 2018

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Background The objective was to study comprehensive mRNA expression profiles of buccal mucosa oral squamous cell carcinoma (OSCC‐BM) and gingivo‐buccal OSCC (OSCC‐GB) in smokeless tobacco chewers to understand the biological behavior of OSCC at these specific sites and identify diagnostic and prognostic markers. Methods High throughput RNA sequencing transcriptome of fresh buccal mucosa (4 samples) and gingivo‐buccal (4 samples) OSCC with normal oral mucosa (3 samples) was performed on Illumina NextSeq500 paired end sequencing with 75x2bp. Results In the comparison between OSCC and normal, there were 402 differentially expressed genes (DEGs); between OSCC‐BM and normal, there were 467 DEGs; and between OSCC‐GB and normal oral tissue, there were 608 DEGs. Pathway‐based analysis of gene expression was done. The inflammation mediated by chemokine and cytokine signaling pathway had the maximum gene hits. Conclusions FZD2 and its interactions with the cadherins have a role in invasion and metastasis. immunosurveillance is evident in OSCC‐GB with the downregulation of CADM1.

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Frizzled2 mediates the migration and invasion of human oral squamous cell carcinoma cells through the regulation of the signal transducer and activator of transcription-3 signaling pathway

Cited by 20 publications

References 35 publications

Promotion of epithelial-mesenchymal transition by Frizzled2 is involved in the metastasis of endometrial cancer

Promotion of epithelial-mesenchymal transition by Frizzled2 is involved in the metastasis of endometrial cancer

Integrated Genomic and Functional microRNA Analysis Identifies miR-30-5p as a Tumor Suppressor and Potential Therapeutic Nanomedicine in Head and Neck Cancer

Pathway based prognostic gene expression profile of buccal and gingivo‐buccal oral squamous cell carcinoma in smokeless tobacco chewers

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