Vasculogenic mimicry (VM) is the formation of microvascular channels by cancer cells. VM requires cellular processes that are regulated by changes in cellular migration and morphology. Cofilin (CFL), a key regulator of actin depolymerization, has been reported to affect malignant phenotypes of cancer. We show that treatment with inhibitors of actin dynamics suppresses VM in MDA-MB-231 human breast cancer cells. We established CFL-knockout (KO) MDA-MB-231 cells and found that VM was attenuated in CFL-KO cells. Although the re-expression of wild-type CFL restored VM in CFL-KO cells, inactive phosphomimetic CFL failed to do so. Collectively, our results demonstrate that CFL is a critical regulator of VM and implicate CFL as a novel therapeutic target for breast cancer.
Keywords: actin cytoskeleton; breast cancer; cofilin; cytochalasin; jasplakinolide; vasculogenic mimicry.
© 2023 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.