AUTHOR=Yang Mengying , Zhan Yajing , Hou Zhijie , Wang Chunli , Fan Wenjun , Guo Tao , Li Zhuoshi , Fang Lei , Lv Shasha , Li Sisi , Gu Chundong , Ye Mingliang , Qin Hongqiang , Liu Quentin , Cui Xiaonan TITLE=VLDLR disturbs quiescence of breast cancer stem cells in a ligand-independent function JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.887035 DOI=10.3389/fonc.2022.887035 ISSN=2234-943X ABSTRACT=

Breast cancer stem cells are responsible for cancer initiation, progression, and drug resistance. However, effective targeting strategies against the cell subpopulation are still limited. Here, we unveil two splice variants of very-low-density lipoprotein receptor, VLDLR-I and -II, which are highly expressed in breast cancer stem cells. In breast cancer cells, VLDLR silencing suppresses sphere formation abilities in vitro and tumor growth in vivo. We find that VLDLR knockdown induces transition from self-renewal to quiescence. Surprisingly, ligand-binding activity is not involved in the cancer-promoting functions of VLDLR-I and -II. Proteomic analysis reveals that citrate cycle and ribosome biogenesis-related proteins are upregulated in VLDLR-I and -II overexpressed cells, suggesting that VLDLR dysregulation is associated with metabolic and anabolic regulation. Moreover, high expression of VLDLR in breast cancer tissues correlates with poor prognosis of patients. Collectively, these findings indicate that VLDLR may be an important therapeutic target for breast cancer treatment.