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Fabrication of Tongue Extracellular Matrix and Reconstitution of Tongue Squamous Cell Carcinoma In Vitro
Published on: June 20, 2018
SCUBE3 Exerts a Tumor-Promoting Effect in Tongue Squamous Cell Carcinoma by Promoting CEBPA Binding to the CCL2
Minhui Zhu1, Yi Ma1, Wei Wang1
1Department of Otorhinolaryngology-Head and Neck Surgery, Changhai Hospital, Naval Medical University, Shanghai, P.R. China.
Abstract:
Tongue squamous cell carcinoma (TSCC) is the main pathologic subtype of oral cancer, and the current therapeutic effect is far from satisfactory. The signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) has been shown to be a tumor-promoting factor in several malignancies. However, little is known about the role of SCUBE3 in TSCC. In this study, we identified that SCUBE3 was highly expressed in TSCC. Clinically, high expression of SCUBE3 was positively associated with tumor stage and T stage of TSCC. Functionally, SCUBE3 silence remarkably restrained cell proliferation, migration, and invasion, induced apoptosis as well as cell cycle arrest in G2-phase, and weakened the tumorigenicity of TSCC cells in vivo. Mechanistically, SCUBE3 promoted the direct binding of CCAAT enhancer binding protein alpha (CEBPA) to C-C motif chemokine ligand 2 (CCL2) promoter in TSCC cells. Interestingly, CCL2 overexpression partially reversed the inhibitory effect of SCUBE3 deficiency on TSCC cell viability and migration. Moreover, STAT3 signaling contributed to CCL2-mediated phenotypes in TSCC cells.
Implications:
Our data revealed a tumor-promoting role for SCUBE3 in TSCC via the CEBPA/CCL2/STAT3 axis, which provided new insight into novel potential therapeutic target for TSCC.
Insights
Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) promotes tongue squamous cell carcinoma (TSCC) growth. Targeting the SCUBE3/CEBPA/CCL2/STAT3 pathway may offer new therapeutic strategies for oral cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Tongue squamous cell carcinoma (TSCC) is a major oral cancer subtype with limited treatment options.
- Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) is implicated in various cancers, but its role in TSCC is unclear.
Purpose of the Study:
- To investigate the expression and function of SCUBE3 in TSCC.
- To elucidate the underlying molecular mechanisms of SCUBE3 in TSCC progression.
Main Methods:
- Analysis of SCUBE3 expression in TSCC tissues.
- In vitro experiments involving SCUBE3 knockdown and CCL2 overexpression in TSCC cells.
- In vivo tumorigenicity assays.
- Western blotting and promoter binding assays to explore molecular pathways.
Main Results:
- SCUBE3 is highly expressed in TSCC, correlating with advanced tumor and T stages.
- SCUBE3 silencing inhibited TSCC cell proliferation, migration, invasion, and in vivo tumor growth, while inducing apoptosis and G2-phase cell cycle arrest.
- SCUBE3 promotes TSCC by facilitating CEBPA binding to the CCL2 promoter, activating the CCL2/STAT3 signaling axis.
Conclusions:
- SCUBE3 acts as a tumor promoter in TSCC through the CEBPA/CCL2/STAT3 pathway.
- SCUBE3 represents a potential therapeutic target for TSCC, offering new avenues for oral cancer treatment.
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