E2F8-CENPL pathway contributes to homologous recombination repair and chemoresistance in breast cancer.

Abstract

Chemoresistance poses a significant obstacle to the treatment of breast cancer patients. The increased capacity of DNA damage repair is one of the mechanisms underlying chemoresistance. Bioinformatic analyses showed that E2F8 was associated with cell cycle progression and homologous recombination (HR) repair of DNA double-strand breaks (DSBs) in breast cancer. E2F8 knockdown suppressed cell growth and attenuated HR repair. Accordingly, E2F8 knockdown sensitized cancer cells to Adriamycin and Cisplatin. Centromere protein L (CENPL) is a transcriptional target by E2F8. CENPL overexpression in E2F8-knockdowned cells recovered at least in part the effect of E2F8 on DNA damage repair and chemotherapy sensitivity. Consistently, CENPL knockdown impaired DNA damage repair and sensitized cancer cells to DNA-damaging drugs. These findings demonstrate that targeting E2F8-CENPL pathway is a potential approach to overcoming chemoresistance.

• Authors: Shan Wang, Yuhong Xia, Yu Sun, Wei Wang, Lianfeng Shan, Zhongbo Zhang, Chenghai Zhao
• Journal: Cellular signalling (Cell Signal) Vol. 118 Pg. 111151 (Jun 2024) ISSN: 1873-3913 [Electronic] England
• PMID: 38522807 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 Elsevier Inc. All rights reserved.

Chemical References

• DNA
• E2F8 protein, human
• Repressor Proteins
• CENPL protein, human
• Chromosomal Proteins, Non-Histone
• Cell Cycle Proteins

Topics

• Humans
• Female
• Recombinational DNA Repair
• Breast Neoplasms (drug therapy, genetics)
• Drug Resistance, Neoplasm (genetics)
• DNA Repair
• DNA
• Repressor Proteins (genetics)
• Chromosomal Proteins, Non-Histone
• Cell Cycle Proteins (genetics)