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.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Lin CC,Lo MC,Moody R,Jiang H,Harouaka R,Stevers N,Tinsley S,Gasparyan M,Wicha M,Sun Ddoi
10.1016/j.canlet.2018.09.022subject
Has Abstractpub_date
2018-12-01 00:00:00pages
165-173eissn
0304-3835issn
1872-7980pii
S0304-3835(18)30577-9journal_volume
438pub_type
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