F-box and Leucine-rich Repeat Protein 16 Controls Tamoxifen Sensitivity Via Regulation of Mitochondrial Respiration in Estrogen Receptor-positive Breast Cancer Cells

Overview

Journal Hum Cell

Publisher Springer

Specialty Cell Biology

Date 2023 Aug 3

PMID 37537406

Authors

Feng Chen

Lu Wang

Yanrong Feng

Wenxin Ma

Junqin Liu

Qianyao Bi

Yao Song

Rui Gao

Yanhan Jia

Affiliations

Soon will be listed here.

Abstract

Tamoxifen is one of the most effective therapeutic tools for estrogen receptor-positive (ER +) breast cancer. However, the intrinsic insensitivity and resistance to tamoxifen remains a significant hurdle for achieving optimal responses and curative therapy. In this study, we report that F-box and leucine-rich repeat protein 16 (FBXL16) is located in the mitochondria of ER + breast cancer cells. The mitochondrial FBXL16 plays an essential role in sustaining mitochondrial respiration and thereby regulates the sensitivity of ER + breast cancer cells to tamoxifen treatment. Importantly, high FBXL16 expression is significantly correlated with poor overall survival of ER + breast cancer patients. Moreover, mitochondrial inhibition phenocopies FBXL16 depletion in terms of sensitizing the ER + breast cancer cells to tamoxifen treatment. Together, our study demonstrates that FBXL16 acts as a novel regulator of tamoxifen sensitivity. Thus, targeting FBXL16 may serve as a promising approach for improving the therapeutic efficacy of tamoxifen in ER + breast cancer cells.

Citing Articles

Functional analysis of the effects of propofol on tamoxifen‑resistant breast cancer cells: Insights into transcriptional regulation.

Yin R, Gao J, Liu Y, Guo C Oncol Lett. 2025; 29(4):194.

PMID: 40041408 PMC: 11878209. DOI: 10.3892/ol.2025.14940.

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