Targeted Intervention of NF2-YAP Signaling Axis in CD24-Overexpressing Cells Contributes to Encouraging Therapeutic...

Area of Science:

• Oncology
• Cancer Biology
• Nanomedicine

Background:

• Triple-negative breast cancer (TNBC) lacks effective classification and targeted therapies, leading to high recurrence and metastasis.
• CD24high cells constitute the majority of TNBC, exhibiting resistance to conventional chemotherapy (Taxol) but sensitivity to ferroptosis.
• These CD24high cells evade phagocytosis by tumor-associated macrophages, contributing to tumor progression.

Purpose of the Study:

• To investigate the role of the NF2-YAP signaling axis in CD24high TNBC cells.
• To develop a precision targeted therapy system for CD24high TNBC cells.
• To enhance ferroptosis and macrophage phagocytosis for improved TNBC treatment.

Main Methods:

• Characterization of CD24high TNBC cells and their sensitivity to ferroptosis agonists.
• Analysis of the NF2-YAP signaling pathway's role in regulating FSP1 and CD24 expression.
• Design and evaluation of a pH- and glutathione-responsive nanoprecision treatment system targeting CD24high cells.

Main Results:

• The NF2-YAP signaling axis was identified as a modulator of FSP1 and CD24 expression in CD24high cells, influencing ferroptosis and macrophage phagocytosis.
• The developed nanoprecision system effectively targeted CD24high cells, inducing lysosomal escape and drug release via CO2 production.
• This targeted system enhanced ferroptosis and macrophage phagocytosis by inhibiting FSP1 and CD24, leading to significant TNBC tumor inhibition.

Conclusions:

• The NF2-YAP signaling axis is a critical regulator in CD24high TNBC, impacting ferroptosis and immune evasion.
• A novel nanoprecision treatment system demonstrates efficacy in targeting CD24high TNBC cells.
• This therapeutic strategy offers a promising approach for treating TNBC by inducing dual antitumor effects.