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STEAP1 Suppresses Oral Squamous Cell Carcinoma by Targeting Wnt/β-Catenin Signalling and EMT
Kuangyu Jin1, Shitong Liu1, Hui Jin1
1The First Affiliated Hospital of Harbin Medical University, Harbin Medical University, School of Stomatology, Harbin, China.
Objective:
The present study aimed to investigate the expression and biological behaviour of the six-transmembrane epithelial antigen of the prostate 1 (STEAP1) in oral squamous cell carcinoma (OSCC), and to further analyse its underlying mechanisms.
Material And Methods:
Western blot and immunohistochemistry were used to detect protein expression. After overexpression of STEAP1 in OSCC cells by plasmid transfection, cell proliferation, migration, and invasion abilities were assessed using CCK-8, scratch, and Transwell assays, respectively, and ROS levels were detected using the corresponding kits. Finally, the expression changes of EMT and Wnt/β-catenin pathway-related proteins were analysed by Western blot.
Result:
Western blot (WB) and immunohistochemical (IHC) analyses showed that STEAP1 was significantly underexpressed (p < 0.0001) in oral squamous cell carcinoma (OSCC) tissues and cell lines (SAS, Tca-8113, SCC15) compared to normal controls. Functional experiments showed that overexpression of STEAP1 effectively inhibited the proliferation (p < 0.001), migration (p < 0.0001), and invasion (p < 0.001) abilities of OSCC cells (SAS, Tca-8113) and reduced intracellular ROS levels (p < 0.0001). Molecularly, STEAP1 overexpression up-regulated E-cadherin (p < 0.01) and down-regulated N-cadherin (p < 0.05), inhibiting the EMT process; meanwhile, it decreased the protein levels of β-catenin (p < 0.05), Axin2 (p < 0.05), and c-Myc (p < 0.05), as well as the protein levels of the p- GSK3β/T-GSK3β ratio (p < 0.05), but there was no significant change in total GSK3β protein, suggesting inhibition of the Wnt/β-catenin pathway.
Conclusion:
STEAP1 is downregulated in OSCC and suppresses malignant phenotypes of OSCC cells in vitro, with effects associated with EMT-related changes and attenuation of Wnt/β-catenin-associated signalling.
Insights
Six-transmembrane epithelial antigen of the prostate 1 (STEAP1) is underexpressed in oral squamous cell carcinoma (OSCC). Restoring STEAP1 inhibits OSCC cell proliferation, migration, and invasion by affecting EMT and Wnt/β-catenin signaling.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Oral squamous cell carcinoma (OSCC) is a prevalent malignancy with complex molecular underpinnings.
- The role of six-transmembrane epithelial antigen of the prostate 1 (STEAP1) in OSCC progression remains incompletely understood.
Purpose of the Study:
- To investigate the expression profile of STEAP1 in OSCC.
- To elucidate the functional impact of STEAP1 on OSCC cell behavior.
- To analyze the molecular mechanisms, including epithelial-mesenchymal transition (EMT) and Wnt/β-catenin signaling, influenced by STEAP1.
Main Methods:
- Protein expression analysis using Western blot (WB) and immunohistochemistry (IHC).
- Functional assays (CCK-8, scratch, Transwell) to assess proliferation, migration, and invasion upon STEAP1 overexpression.
- Detection of reactive oxygen species (ROS) levels.
- Analysis of EMT and Wnt/β-catenin pathway-related protein expression via WB.
Main Results:
- STEAP1 was significantly downregulated in OSCC tissues and cell lines compared to normal controls.
- Overexpression of STEAP1 suppressed OSCC cell proliferation, migration, and invasion, and reduced intracellular ROS levels.
- STEAP1 overexpression inhibited EMT by upregulating E-cadherin and downregulating N-cadherin.
- STEAP1 modulated Wnt/β-catenin pathway components, including decreased β-catenin, Axin2, c-Myc, and altered p-GSK3β/T-GSK3β ratio, indicating pathway inhibition.
Conclusions:
- STEAP1 exhibits tumor-suppressive functions in OSCC.
- Downregulation of STEAP1 contributes to the malignant phenotype of OSCC.
- STEAP1 exerts its effects through modulation of EMT and attenuation of Wnt/β-catenin signaling.
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