Published online Jul 16, 2023. doi: 10.12998/wjcc.v11.i20.4788
Peer-review started: March 20, 2023
First decision: April 11, 2023
Revised: April 24, 2023
Accepted: June 13, 2023
Article in press: June 13, 2023
Published online: July 16, 2023
Tamoxifen (TAM) resistance is a major obstacle in the treatment of breast cancer (BC) patients. It has been reported that eukaryotic translation initiation factor 4E binding protein 1 (EIF4EBP1) plays critical roles in the tumorigenesis and development of BC.
TAM resistance remains one of the major causes of BC mortality today. Therefore, it is necessary to identify biomarkers and therapeutic targets and understand molecular mechanisms of TAM resistance to help patients.
The objective was to investigate the expression and functions of EIF4EBP1 in the efficacy of TAM therapy in BC patients.
Gene Set Enrichment Analysis (GSEA) was performed to explore the biological functions and related pathways of EIF4EBP1. Real-time reverse transcription polymerase chain reaction were employed to explore the expression of EIF4EBP1 in TAM-resistant and TAM-sensitive BC cell lines. Cell count kit-8 assay, colony formation experiments and the wound healing assay were used to understand the phenotypes of loss- and gain-of-function of EIF4EBP1 in a TAM-resistant cell line.
EIF4EBP1 was upregulated in TAM resistant cells, and EIF4EBP1 was associated with the prognosis of BC patients. GSEA suggested that EIF4EBP1 may be involved in the Hedgehog signaling pathway. Reducing the expression of EIF4EBP1 can reverse TAM resistance, while overexpression of EIF4EBP2 can promote TAM resistance.
In this study, we investigated the role of EIF4EBP1 in TAM resistance. Scholars have performed studies on the role of EIF4EBP1 in TAM resistance, and their conclusions of these studies were similar with no controversy. However, most of these conclusions were based on bioinformatics analysis. The role of EIF4EBP1 in TAM resistance has not been experimentally demonstrated. This study indicated that EIF4EBP1 enhanced the resistance of T47D-R cells to TAM. In addition, our GSEA results may provide new insights into the molecular mechanism of TAM resistance. In brief, EIF4EBP1 could be a marker for the early diagnosis and a therapeutic target for the therapy of TAM resistance.
Further studies should explore the potential function and molecular mechanism of EIF4EBP1 in TAM-resistant BC cells through in vitro and in vivo experiments.