Redundant and Non-Redundant Functions of Actin Depolymerizing Factor (ADF) and Cofilin in Metastasis- Review

Tumor cell motility is the hallmark of invasion and an essential step in metastasis. Cellular changes that occur during the progression of cancer affect proteins that drive actin dynamics; these changes modulate cell cycle progression and lead to more invasive cancers. Actin depolymerizing factor (ADF)/cofilins (actin dynamizing proteins) and their regulatory proteins are involved in the initiation of early steps in cell motility. ADF/cofilins play important roles in various stages of cancer progression including cell polarization and polarized migration, escape from apoptosis, and secretion of metalloproteases, all of which are important in metastasis. Vertebrates express ADF, cofilin-1 and cofilin-2, and even though ADF and cofilin have many qualitatively similar biochemical properties, they differ quantitatively in actin interaction and in some types of regulation and, thus, are not functionally identical. This review compares the activities of these two proteins with respect to how they may function during tumor cell invasion. Understanding the molecular pathways of tumor invasion will provide new diagnostic approaches and targets for the treatment of metastatic cancer.