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

## TL;DR

This study finds that fibronectin, a protein linked to cancer spread and immune evasion, is a shared target in oral and breast cancers, suggesting it could be used for new treatments.

## Contribution

FN1 is identified as a shared EMT-related gene in oral and breast carcinomas, linked to immune suppression and tumor progression.

## Key findings

- EMT-related genes are strongly associated with immunosuppressive macrophages in both OSCC and BC.
- FN1 gene expression is elevated in OSCC and BC tissues compared to normal tissues.
- FN1 is a potential therapeutic target for both OSCC and BC due to its role in tumor invasion and immune evasion.

## Abstract

The tightly controlled and transient acquisition of a motile phenotype by otherwise static epithelial cells (epithelial–mesenchymal transition, EMT) enables the repair of a damaged epithelium. Conversely, a persistent, dysregulated, and exacerbated EMT characterizes epithelial malignancies such as breast carcinoma (BC) and oral squamous cell carcinoma (OSCC), being key for their metastasis and for their escaping anti-tumor immune responses. Herein, we investigated the relationship between EMT signatures and immune cell infiltration across OSCC and metastatic BC with the aim to identify prognostic markers and/or therapeutic targets common to both these malignancies, or unique to OSCC or BC. To this end, we analyzed publicly available transcriptomic datasets to identify coding genes involved in EMT with strong correlation to immune cell signatures. The methodology consisted of data selection, correlation analysis, signature overlap determination, and validation using independent databases. Results indicated that in both OSCC and BC the expression of EMT-related genes is strongly associated with that of immunosuppressive and pro-tumor macrophages. Notably, the FN1 gene coding for the extracellular matrix glycoprotein fibronectin (FN) emerged as the EMT gene common to either tumor types. In confirmation of this, FN protein levels were higher in OSCC and BC tissues than in their normal counterparts. Given FN capability of favoring tumor invasion and metastasis while hindering antitumor immune responses, these data encourage the development of FN antagonists to be used as an adjunct to conventional therapy in the treatment of both OSCC and BC.