# Fbxo45 facilitates the malignant progression of breast cancer by targeting Bim for ubiquitination and degradation

## TL;DR

This study shows that FBXO45 promotes breast cancer by breaking down BIM, suggesting targeting this pathway could help treat the disease.

## Contribution

The novel finding is that FBXO45 targets BIM for ubiquitination and degradation, driving breast cancer progression.

## Key findings

- Downregulation of FBXO45 inhibits breast cancer cell proliferation and induces apoptosis.
- FBXO45 interacts with BIM and regulates its ubiquitination and degradation.
- Overexpression of FBXO45 is associated with poor survival in breast cancer patients.

## Abstract

Breast cancer is one of the common malignancies in women. Evidence has demonstrated that FBXO45 plays a pivotal role in oncogenesis and progression. However, the role of FBXO45 in breast tumorigenesis remains elusive. Exploration of the regulatory mechanisms of FBXO45 in breast cancer development is pivotal for potential therapeutic interventions in patients with breast cancer.

Hence, we used numerous approaches to explore the functions of FBXO45 and its underlaying mechanisms in breast cancer pathogenesis, including CCK-8 assay, EdU assay, colony formation analysis, apoptosis assay, RT-PCR, Western blotting, immunoprecipitation, ubiquitination assay, and cycloheximide chase assay.

We found that downregulation of FBXO45 inhibited cell proliferation, while upregulation of FBXO45 elevated cell proliferation in breast cancer. Silencing of FBXO45 induced cell apoptosis, whereas overexpression of FBXO45 inhibited cell apoptosis in breast cancer. Moreover, FBXO45 interacted with BIM and regulated its ubiquitination and degradation. Furthermore, knockdown of FBXO45 inhibited cell proliferation via regulation of BIM pathway. Notably, overexpression of FBXO45 facilitated tumor growth in mice. Strikingly, FBXO45 expression was associated with poor survival of breast cancer patients.

Our study could provide the rational for targeting FBXO45 to obtain benefit for breast cancer patients. Altogether, modulating FBXO45/Bim axis could be a promising strategy for breast cancer therapy.

The online version contains supplementary material available at 10.1186/s12885-024-12382-8.