Leptin-Upregulated Metastasis-Associated Protein 1 Promotes Vasculogenic Mimicry in Breast Cancer Cells

Leptin, a hormone primarily produced by adipose tissue, regulates energy balance and appetite, while contributing significantly to obesity and cancer progression. Vasculogenic mimicry (VM) refers to the process by which aggressive tumor cells form blood vessel-like structures, enabling blood supply independent of endothelial angiogenesis. Metastasis-associated protein 1 (MTA1) facilitates tumor progression and metastasis. This study investigated the role of MTA1 in the relationship between leptin and VM in human breast cancer cells. Leptin upregulated the mRNA and protein expression of MTA1, as revealed by a quantitative real-time PCR and Western blot analysis, respectively. However, the Western blot revealed that leptin-induced MTA1 upregulation was inhibited by the leptin receptor (Ob-R) blocker, Ob-R BP, and the signal transducer and activator of the transcription 3 (STAT3) inhibitor, AG490. The overexpression of MTA1 was observed to induce VM in a three-dimensional culture assay and to upregulate the expression of VM-related proteins, as confirmed by the Western blot. Conversely, silencing MTA1 suppressed leptin-induced VM and the expression of VM-related proteins. These findings indicate that leptin regulates MTA1 expression through the Ob-R/STAT3 signaling pathway and that MTA1 serves as a crucial mediator of leptin-induced VM.