Fetuin-A Modulates Tumor Growth and Invasion in a Basal-like Triple Negative Breast Cancer Cell line, MDA-MB-468

TL;DR

This study shows that fetuin-A increases tumor growth and invasion in a type of breast cancer by interacting with TLR4, suggesting a new target for treatment.

Contribution

The study identifies fetuin-A-TLR4 signaling as a novel driver of growth and invasion in basal-like triple negative breast cancer.

Findings

Fetuin-A overexpression enhances invasive potential and TLR4 expression in MDA-MB-468 cells.

TLR4 inhibition with CLI-095 abrogates fetuin-A-mediated growth and invasion.

Fetuin-A-TLR4 signaling is critical for tumor progression in triple negative breast cancer.

Abstract

The present studies were undertaken to address the innovative role of fetuin-A in the growth and invasion potential in a triple negative breast cancer (TNBC) cell line, MDA-MB-468. Basal like TNBC that express high levels of ectopic fetuin-A have poorer prognosis for the patients compared to those that express low levels of the protein. We overexpressed fetuin-A in MDA-MB-468 and then determined the invasive potential of fetuin-A overexpressing cells vs controls transfected with empty vector. We also determined the adhesion and growth potential of the cells in the presence of only fetuin-A in serum free medium and also in complete medium. Our data suggest that fetuin-A overexpression significantly enhances the invasive potential of the cells and also the expression of Toll like receptor 4 (TLR4) on these cells. More importantly, the cells rely on fetuin-A-TLR4 signaling network for growth and invasion because the specific TLR4 inhibitor CLI-095 (resatorvid) abrogates fetuin-A mediated growth and invasion. Taken together, the data suggest that fetuin-A-TLR4 signaling network plays a significant role in the growth and invasion potential of TNBC.

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