Runx3 inhibits melanoma cell migration through regulation of cell shape change.

Abstract

The transcription factor Runx3 is a known tumor suppressor gene, and its expression is frequently lost in melanoma. However, the potential contribution of the loss of Runx3 expression to melanoma development and progression remains unclear. In this in vitro study, we demonstrated that ectopic Runx3 re-expression in B16-F10 melanoma cells changed the cell shape from elongated and branched to spread and unbranched, which enhanced stress fiber formation, increased the number of mature and fibrillar focal adhesions, and up-regulated fibronectin expression. In association with the cell shape change, the Runx3 re-expression in B16-F10 melanoma cells inhibited cell migration. Moreover, the phenotype of the Runx3 induced cell shape change was partially resembled when the melanoma cells were cultured on a fibronectin-coated coverslip, suggesting that fibronectin may mediate the Runx3 induced cell shape change of the melanoma cells. Taken together, our findings suggest that Runx3 may regulate cell shape to inhibit melanoma cell migration partly through enhancing stress fiber formation and ECM protein production. Our present study provides further evidence for the idea that cell shape change is potentially correlated with melanoma development and progression.