Sphingomyelin synthase 2 promotes the stemness of breast cancer cells via modulating NF-κB signaling pathway

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Multi-drug resistance (MDR) is a major challenge in breast cancer treatment, often leading to metastasis and recurrence.
• Current therapeutic strategies lack effective methods to overcome MDR.
• The role of sphingomyelin synthase 2 (SMS2) in breast cancer resistance remains largely unexplored.

Purpose of the Study:

• To investigate the function of sphingomyelin synthase 2 (SMS2) in the context of breast cancer chemoresistance.
• To elucidate the molecular mechanisms by which SMS2 influences breast cancer cell stemness and drug resistance.

Main Methods:

• Quantitative RT-PCR and Western blot analysis to assess mRNA and protein expression of SMS2.
• CCK-8 assay to determine adriamycin (ADR) inhibitory concentration (IC50) values.
• Spheroid-formation assay to evaluate cancer stem cell properties.
• Immunofluorescence and xenograft mouse models to study protein localization and in vivo effects.

Main Results:

• SMS2 overexpression significantly increased IC50 values, indicating enhanced resistance to ADR.
• SMS2 modulated the expression of stemness markers, decreasing CD24 and increasing CD44, ALDH, OCT 4, and SOX2.
• SMS2 promoted the nuclear translocation of phosphorylated NF-κB, suggesting activation of the NF-κB signaling pathway.

Conclusions:

• SMS2 enhances breast cancer stemness and ADR resistance through the NF-κB signaling pathway.
• SMS2 represents a novel therapeutic target for overcoming chemoresistance in breast cancer.
• This study uncovers a previously unrecognized mechanism in the development of breast cancer MDR.