Targeting LRP8 inhibits breast cancer stem cells in triple-negative breast cancer
| Autor: | Ramdane Harouaka, Rebecca Moody, Nicholas O. Stevers, Miao-Chia Lo, Hui Jiang, Samantha L. Tinsley, Duxin Sun, Chang-Ching Lin, Max S. Wicha, Mari Gasparyan |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Regulator Breast Neoplasms Triple Negative Breast Neoplasms Kaplan-Meier Estimate Mice SCID medicine.disease_cause Metastasis 03 medical and health sciences 0302 clinical medicine Breast cancer Mice Inbred NOD Cell Line Tumor medicine Animals Humans Wnt Signaling Pathway Triple-negative breast cancer LDL-Receptor Related Proteins beta Catenin Gene knockdown business.industry Wnt signaling pathway medicine.disease Xenograft Model Antitumor Assays Tumor Burden 030104 developmental biology HEK293 Cells RNAi Therapeutics Oncology 030220 oncology & carcinogenesis Cancer research Neoplastic Stem Cells Female RNA Interference Stem cell Carcinogenesis business |
| Zdroj: | Cancer letters. 438 |
| ISSN: | 1872-7980 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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