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Updated: Aug 16, 2025
Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
VLDLR disturbs quiescence of breast cancer stem cells in a ligand-independent function
Mengying Yang1,2,3, Yajing Zhan2, Zhijie Hou2
1The First Affiliated Hospital, Dalian Medical University, Dalian, China.
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.
Insights
Two variants of the very-low-density lipoprotein receptor (VLDLR) fuel breast cancer stem cell growth and drug resistance. Targeting VLDLR shows promise for new breast cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Breast cancer stem cells drive tumor initiation, progression, and therapeutic resistance.
- Current strategies for targeting these cells remain limited.
- Identifying novel targets is crucial for effective breast cancer treatment.
Purpose of the Study:
- To investigate the role of very-low-density lipoprotein receptor (VLDLR) splice variants in breast cancer stem cells.
- To explore VLDLR as a potential therapeutic target for breast cancer.
Main Methods:
- Silencing of VLDLR in breast cancer cells.
- Assessment of sphere formation in vitro and tumor growth in vivo.
- Proteomic analysis to identify associated molecular pathways.
Main Results:
- Two VLDLR splice variants, VLDLR-I and -II, are highly expressed in breast cancer stem cells.
- VLDLR silencing inhibits sphere formation, tumor growth, and promotes quiescence.
- VLDLR overexpression is linked to upregulated citrate cycle and ribosome biogenesis proteins.
- VLDLR expression correlates with poor patient prognosis.
Conclusions:
- VLDLR splice variants are key drivers of breast cancer stem cell function.
- VLDLR's role in cancer promotion is independent of its ligand-binding activity.
- VLDLR represents a promising therapeutic target for improving breast cancer treatment outcomes.
