Targeting LRP8 inhibits breast cancer stem cells in triple-negative breast cancer

Cancer Letters
Chang-Ching LinDuxin Sun

Abstract

Triple-negative breast cancer (TNBC) is the most difficult subtype of breast cancer to treat due to a paucity of effective targeted therapies. Many studies have reported that breast cancer stem cells (BCSCs) are enriched in TNBC and are responsible for chemoresistance and metastasis. In this study, we identify LRP8 as a novel positive regulator of BCSCs in TNBC. LRP8 is highly expressed in TNBC compared to other breast cancer subtypes and its genomic locus is amplified in 24% of TNBC tumors. Knockdown of LRP8 in TNBC cell lines inhibits Wnt/β-catenin signaling, decreases BCSCs, and suppresses tumorigenic potential in xenograft models. LRP8 knockdown also induces a more differentiated, luminal-epithelial phenotype and thus sensitizes the TNBC cells to chemotherapy. Together, our study highlights LRP8 as a novel therapeutic target for TNBC as inhibition of LRP8 can attenuate Wnt/β-catenin signaling to suppress BCSCs.

Citations

Aug 7, 2019·Cells·Li Fang NgNicholas S Tolwinski
Apr 24, 2020·Molecular Systems Biology·Monika OberhuberLukas Kenner
Apr 23, 2019·International Journal of Cancer. Journal International Du Cancer·Zhishan WangChengfeng Yang
Aug 28, 2020·Frontiers in Oncology·Océane CampionJérôme Devy
Jul 22, 2019·Cancers·So-Yeon ParkJeong-Seok Nam
May 2, 2020·World Journal of Clinical Oncology·Narges K TafreshiMarie Catherine Lee
Mar 30, 2021·Apoptosis : an International Journal on Programmed Cell Death·Haitao QiuQiaoshu Xu

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