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Updated: Jun 14, 2025
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
STAT3 interactome predicts presence of proteins that regulate immune system in oral squamous cell carcinoma
Rajdeep Chakraborty1, Pallavi Khodlan2, Aidan Tay3
1Applied Biosciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia; School of Natural Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW, 2109, Australia.
Objectives:
Signal transducer and activator of transcription 3 (STAT3) is one of the key proliferation mechanism-related proteins that helps in oral squamous cell carcinoma (OSCC) progression. Immune evasion by STAT3 is mediated by the JAK2/STAT3/PDL1 signaling axis. Based on previous findings, we hypothesized that STAT3-binding partners participate in the inhibition of anti-tumor activity in OSCC.
Methods:
A 3D cancer-immune co-culture model was constructed using oral cancer cell lines SCC4, SCC9, SCC25, and CAL27 and normal oral cell line OKF6. The cells were co-cultured with natural killer (NK-92) and Jurkat cells. The target protein STAT3 was chosen based on SWATH data, and co-immunoprecipitation (Co-IP)-based proteomics was conducted. The Co-IP LC-MS/MS output was analysed to determine the protein interaction network, gene ontology, pathway analysis, and protein cluster annotation.
Results:
STAT3 in oral cancer cell lines interacts with the epidermal growth factor receptor (EGFR) and other proteins that participate in proliferation and immune mechanisms. Proteome analysis showed that some STAT3-binding proteins found in this study are known immune system regulators.
Conclusion:
Overall, STAT3 interactive proteins regulate the immune system in oral squamous cell carcinoma cells.
Insights
Signal transducer and activator of transcription 3 (STAT3) interacts with proteins that drive oral squamous cell carcinoma (OSCC) progression. These STAT3-binding partners are key regulators of the immune system in OSCC.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Signal transducer and activator of transcription 3 (STAT3) is crucial for oral squamous cell carcinoma (OSCC) progression.
- STAT3 facilitates immune evasion in OSCC via the JAK2/STAT3/PDL1 signaling axis.
Purpose of the Study:
- To investigate STAT3-binding partners involved in inhibiting anti-tumor activity in OSCC.
- To elucidate the role of STAT3 interactome in OSCC immune evasion.
Main Methods:
- A 3D cancer-immune co-culture model using OSCC cell lines (SCC4, SCC9, SCC25, CAL27) and normal oral cells (OKF6) with immune cells (NK-92, Jurkat).
- Co-immunoprecipitation (Co-IP)-based proteomics targeting STAT3, followed by LC-MS/MS analysis.
- Bioinformatic analysis including protein interaction network, gene ontology, and pathway analysis.
Main Results:
- STAT3 was found to interact with epidermal growth factor receptor (EGFR) and other proteins involved in proliferation and immune regulation in OSCC cell lines.
- Proteomic analysis identified STAT3-binding proteins that are known regulators of the immune system.
Conclusions:
- STAT3 interactive proteins play a significant role in regulating the immune system within oral squamous cell carcinoma.
- Understanding these interactions may reveal novel therapeutic targets for OSCC.
