ArticleMedical oncology (Northwood, London, England)2022
Fibulin-3 sponges Tiam1 to manipulate MMP-7 activity through β-catenin signaling in oral squamous cell carcinoma.
Article in Medical oncology (Northwood, London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- CAFs-derived TIAM1 Promotes OSCC Cell Growth and Metastasis by Regulating ZEB2.Cell biochemistry and biophysics · 2025Article
- TIMP4 serves as a novel potential prognostic biomarker for oral squamous cell carcinoma.Scientific reports · 2025Article
- Matricellular proteins: Potential biomarkers in head and neck cancer.Journal of cell communication and signaling · 2024Review
- Gut microbiome's causal role in head and neck cancer: findings from mendelian randomization.Frontiers in oncology · 2024Article
- Impact of Rehydration Following Systemic Dehydration on Vocal Fold Gene Expression.The Laryngoscope · 2023Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Oral squamous cell carcinoma (named OSCC) is considered the most frequent malignancy in oral cavity, which has become a rapid increasing problem for the global public health with unclear molecular mechanism. Previously, Tiam1 (T-lymphoma invasion and metastasis inducing factor 1) has been reported as a potential oncogene for OSCC. Here, we in-depth explored its signaling mechanism for the disorder. The mRNA and protein expression levels of primary differentially expressed genes (Tiam1, Fibulin-3, and MMP-7) were measured in different TNM stages of OSCC patients using RT-PCR and ELISA methods. Based on the analysis of human OSCC cell line CAL27, the relationships between these factors have been further investigated and the interactions were also examined. The luciferase reporter assay was established for the promoter region of MMP-7. Both the epithelial (E-cadherin) and mesenchymal protein markers (Vimentin and Snail) expressions were examined using western blotting. The mRNA and protein activities of Fibulin-3 declined as the increase of TNM stage. Inversely, the mRNA and protein levels of Tiam1 and MMP-7 elevated significantly as OSCC progressed. Tiam1 transfection in CAL27 cells stimulated the expression of MMP-7 by accelerating the nuclear translocation of β-catenin, which was opposite to the functions of Fibulin-3. Moreover, Tiam1 interacted directly with Fibulin-3. The Tiam1 induced OSCC epithelial-mesenchymal transition (EMT) via MMP-7 activation, which was dependent on the direct binding of β-catenin at the promoter region. Collectively, these results indicated that Tiam1 competed with Fibulin-3 for nuclear β-catenin translocation, which subsequently stimulated MMP-7 expression by TCF-4 domain interaction following EMT initiation in OSCC development. Our systematical work hypothesized an innovative signaling cassette for OSCC progression, which provided beneficial references for future clinical study.
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