CDCA5 Accelerates Progression of Breast Cancer by Promoting the Binding of E2F1 and FOXM1

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2024 Jul 8

PMID 38978058

Authors

Yiquan Xiong

Lan Shi

Lei Li

Wen Yang

Huiqiong Zhang

Xiangwang Zhao

Na Shen

Affiliations

Soon will be listed here.

Abstract

Background: Breast cancer is one of the most common malignant tumors in women. Cell division cycle associated 5 (CDCA5), a master regulator of sister chromatid cohesion, was reported to be upregulated in several types of cancer. Here, the function and regulation mechanism of CDCA5 in breast cancer were explored.

Methods: CDCA5 expression was identified through immunohistochemistry staining in breast cancer specimens. The correlation between CDCA5 expression with clinicopathological features and prognosis of breast cancer patients was analyzed using a tissue microarray. CDCA5 function in breast cancer was explored in CDCA5-overexpressed/knockdown cells and mice models. Co-IP, ChIP and dual-luciferase reporter assay assays were performed to clarify underlying molecular mechanisms.

Results: We found that CDCA5 was expressed at a higher level in breast cancer tissues and cell lines, and overexpression of CDCA5 was significantly associated with poor prognosis of patients with breast cancer. Moreover, CDCA5 knockdown significantly suppressed the proliferation and migration, while promoted apoptosis in vitro. Mechanistically, we revealed that CDCA5 played an important role in promoting the binding of E2F transcription factor 1 (E2F1) to the forkhead box M1 (FOXM1) promoter. Furthermore, the data of in vitro and in vivo revealed that depletion of FOXM1 alleviated the effect of CDCA5 overexpression on breast cancer. Additionally, we revealed that the Wnt/β-catenin signaling pathway was required for CDCA5 induced progression of breast cancer.

Conclusions: We suggested that CDCA5 promoted progression of breast cancer via CDCA5/FOXM1/Wnt axis, CDCA5 might serve as a novel therapeutic target for breast cancer treatment.

Citing Articles

E2F1-Dependent CDCA5 overexpression drives cervical cancer progression and correlates with poor prognosis.

Wang Y, Zhang W, Peng M J Mol Histol. 2025; 56(2):80.

PMID: 39907709 DOI: 10.1007/s10735-025-10356-z.

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