FZD5 Contributes to TNBC Proliferation, DNA Damage Repair and Stemness

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2020 Dec 14

PMID 33311446

Citations 18

Authors

Yu Sun

Zhuo Wang

Lei Na

Dan Dong

Wei Wang

Chenghai Zhao

Affiliations

Soon will be listed here.

Abstract

Chemotherapy currently remains the standard treatment for triple-negative breast cancer (TNBC). However, TNBC frequently develop chemoresistance, which is responsible for cancer recurrence and distal metastasis. Both DNA damage repair and stemness are related to chemoresistance. FZD5, a member in Frizzled family, was identified to be preferentially expressed in TNBC, and associated with unfavorable prognosis. Loss and gain of function studies revealed that FZD5 contributed to TNBC cell G1/S transition, DNA replication, DNA damage repair, survival, and stemness. Mechanistically, transcription factor FOXM1, which promoted BRCA1 and BIRC5 transcription, acted as a downstream effecter of FZD5 signaling. FOXM1 overexpression in FZD5-deficient/low TNBC cells induced FZD5-associated phenotype. Finally, Wnt7B, a specific ligand for FZD5, was shown to be involved in cell proliferation, DNA damage repair, and stemness. Taken together, FZD5 is a novel target for the development of therapeutic strategies to overcome chemoresistance and prevent recurrence in TNBC.

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