# The Combination of MIF Inhibitor and AEP Targeted Inhibitor to Reduce Lung Metastasis in Breast Cancer and Its Mechanism

## TL;DR

This study explores how combining two inhibitors can reduce lung metastasis in breast cancer by targeting AEP and CD74, offering a new treatment approach.

## Contribution

The study identifies a novel therapeutic strategy using dual inhibition of AEP and CD74 to suppress breast cancer metastasis.

## Key findings

- AEP activates the ERK pathway via CD74 regulation, promoting epithelial-mesenchymal transition and cancer cell migration.
- Dual inhibition of AEP and CD74 reduced EMT markers and cancer cell migration in vitro.
- Combining AEP and CD74 inhibitors significantly suppressed lung metastasis in mice without toxicity.

## Abstract

Breast cancer, the most prevalent malignant tumour in women, is characterised by high metastatic potential and frequent recurrence, both of which significantly impact patient prognosis following metastasis. To address this challenge, identifying novel therapeutic target combinations is critical for improving metastatic breast cancer treatment. This study investigates the mechanism by which asparaginyl endopeptidase (AEP) regulates breast cancer metastasis. Bioinformatics analysis revealed a potential interaction between AEP and CD74, which was subsequently confirmed through co‐immunoprecipitation (co‐IP) experiments. Further investigations demonstrated that AEP activates ERK pathway phosphorylation via CD74 regulation, thereby enhancing epithelial‐mesenchymal transition (EMT) progression and promoting breast cancer cell migration. Compared to controls, dual inhibition of AEP and CD74 effectively reduced EMT markers and the migratory capacity of cancer cells in vitro. Subsequent in vivo experiments showed that this combinatorial strategy significantly suppressed breast cancer lung metastasis in mice without observable toxicity. These findings elucidate the molecular mechanism through which AEP promotes metastasis via CD74 regulation, while validating the therapeutic efficacy and safety of dual AEP/CD74 targeting. This study provides a novel conceptual framework and potential therapeutic targets for metastatic breast cancer intervention.