Fibronectin Is a Likely Therapeutic Target Shared by Oral and Breast Carcinomas

Area of Science:

• Oncology
• Cell Biology
• Immunology

Background:

• Epithelial-mesenchymal transition (EMT) is crucial for epithelial repair but drives cancer progression, metastasis, and immune evasion in malignancies like breast carcinoma (BC) and oral squamous cell carcinoma (OSCC).
• Understanding the interplay between EMT and the tumor immune microenvironment is vital for identifying new therapeutic strategies.
• Dysregulated EMT contributes to the aggressiveness of OSCC and BC.

Purpose of the Study:

• To investigate the relationship between EMT signatures and immune cell infiltration in OSCC and metastatic BC.
• To identify common or unique prognostic markers and therapeutic targets for OSCC and BC related to EMT and immune responses.
• To explore the role of specific EMT-related genes in immune modulation within these cancers.

Main Methods:

• Analysis of publicly available transcriptomic datasets for OSCC and metastatic BC.
• Identification of coding genes involved in EMT with strong correlations to immune cell signatures.
• Correlation analysis, signature overlap determination, and validation using independent databases.

Main Results:

• EMT-related gene expression strongly correlates with immunosuppressive and pro-tumor macrophages in both OSCC and BC.
• The *FN1* gene, encoding fibronectin (FN), emerged as a common EMT gene in both tumor types.
• Elevated FN protein levels were observed in OSCC and BC tissues compared to normal tissues, supporting its role in cancer progression.

Conclusions:

• Fibronectin (FN) plays a significant role in promoting tumor invasion, metastasis, and hindering anti-tumor immune responses in both OSCC and BC.
• Targeting FN through antagonists could be a promising adjunct therapy for treating OSCC and BC.
• The study identifies FN as a potential common therapeutic target for these distinct epithelial malignancies.