Oleate Promotes Triple-Negative Breast Cancer Cell Migration by Enhancing Filopodia Formation through a...

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Triple-negative breast cancer (TNBC) is a global health concern with limited treatment options.
• Elevated stearoyl-CoA desaturase 1 (SCD1) and its product oleate (OA) are linked to cancer progression and metastasis.
• The precise molecular mechanisms by which OA influences TNBC cell migration are not fully understood.

Purpose of the Study:

• To investigate the impact of oleate (OA) on actin remodeling and signaling pathways in TNBC cell lines.
• To elucidate the role of OA in cell migration and identify key molecular players involved.

Main Methods:

• Utilized TNBC cell lines and bioinformatics tools.
• Stimulated cells with OA and analyzed actin structure, cell morphology, and protein translocation.
• Employed inhibition studies targeting Arp2/3 complex and Cdc42.
• Investigated the involvement of phospholipase D.

Main Results:

• OA stimulation induced rapid cell membrane ruffling and enhanced filopodia formation in TNBC cells.
• OA treatment triggered the translocation of Arp2/3 complex and Cdc42.
• Inhibition of Cdc42, but not Arp2/3, abolished OA-induced filopodia formation and cell migration.
• Phospholipase D was implicated in Cdc42-dependent migration.
• Elevated Cdc42 expression in breast tumors correlated with lower patient survival.

Conclusions:

• OA promotes TNBC cell migration via Cdc42-dependent filopodia formation, revealing a novel signaling pathway.
• Cdc42 is a critical mediator of OA-induced migration in TNBC.
• This pathway presents a potential therapeutic target for TNBC treatment.