FOXM1 contributes to taxane resistance by regulating UHRF1-controlled cancer cell stemness

Cell Death & Disease
Bowen YuanXiong Li

Abstract

Therapy-induced expansion of cancer stem cells (CSCs) has been identified as one of the most critical factors contributing to therapeutic resistance, but the mechanisms of this adaptation are not fully understood. UHRF1 is a key epigenetic regulator responsible for therapeutic resistance, and controls the self-renewal of stem cells. In the present study, taxane-resistant cancer cells were established and stem-like cancer cells were expanded. UHRF1 was overexpressed in the taxane-resistant cancer cells, which maintained CSC characteristics. UHRF1 depletion overcame taxane resistance in vitro and in vivo. Additionally, FOXM1 has been reported to play a role in therapeutic resistance and the self-renewal of CSCs. FOXM1 and UHRF1 are highly correlated in prostate cancer tissues and cells, FOXM1 regulates CSCs by regulating uhrf1 gene transcription in an E2F-independent manner, and FOXM1 protein directly binds to the FKH motifs at the uhrf1 gene promoter. This present study clarified a novel mechanism by which FOXM1 controls CSCs and taxane resistance through a UHRF1-mediated signaling pathway, and validated FOXM1 and UHRF1 as two potential therapeutic targets to overcome taxane resistance.

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Citations

Jul 16, 2020·Journal of Cellular and Molecular Medicine·Wen-Jing ZengXiao-Ping Chen
Jan 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Spencer AsayJason D Kenealey
Dec 10, 2020·Cancer Cell International·Hongbo YuJianzhong Lin
Feb 17, 2021·Acta Pharmacologica Sinica·Yi-Xin ChenZhao-Qian Liu
Aug 19, 2021·Nature Communications·Julea VlassakisAmy E Herr

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Methods Mentioned

BETA
flow cytometry
transfection
xenografts
Assay
PCR
ChIP-PCR
xenograft
ChIP-seq
immunoprecipitation

Software Mentioned

Genomic Data Commons ( GDC
GraphPad

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