Peer review process
Not revised: This Reviewed Preprint includes the authors’ original preprint (without revision), an eLife assessment, and public reviews.
Read more about eLife’s peer review process.Editors
- Reviewing EditorYaoting JiWuhan University, Wuhan, China
- Senior EditorCaigang LiuShengjing Hospital of China Medical University, Shenyang, China
Reviewer #1 (Public review):
Summary:
Tamoxifen resistance is a common problem in partially ER-positive patients undergoing endocrine therapy, and this manuscript has important research significance as it is based on clinical practical issues. The manuscript discovered that the absence of FRMD8 in breast epithelial cells can promote the progression of breast cancer, thus proposing the hypothesis that FRMD8 affects tamoxifen resistance and validating this hypothesis through a series of experiments. The manuscript has a certain theoretical reference value.
Strengths:
At present, research on the role of FRMD8 in breast cancer is very limited. This manuscript leverages the MMTV-Cre+;Frmd8fl/fl;PyMT mouse model to study the role of FRMD8 in tamoxifen resistance, and single-cell sequencing technology discovered the interaction between FRMD8 and ESR1. At the mechanistic level, this manuscript has demonstrated two ways in which FRMD8 affects ERα, providing some new insights into the development of ER-positive breast cancer in patients who are resistant to tamoxifen.
Weaknesses:
This manuscript repeatedly emphasizes the role of FRMD8/FOXO3A in tamoxifen resistance in ER-positive breast cancer, but the specific mechanisms have not yet been fully elucidated. Whether FRMD8 can become a biomarker should be verified in large clinical samples or clinical data.
Reviewer #2 (Public review):
Summary:
The manuscript presents a valuable finding on the impact of FRMD8 loss on tumor progression and the resistance to tamoxifen therapy. The author conducted systematic experiments to explore the role of FRMD8 in breast cancer and its potential regulatory mechanisms, confirming that FRMD8 could serve as a potential target to revere tamoxifen resistance.
Strengths:
The majority of the research is logically clear, smooth, and persuasive.
Weaknesses:
Some research in the article lacks depth and some sentences are poorly organized.
