Profilin-1 mediated cell-cycle arrest: searching for drug targets

Abstract

Proliferation, resistance to apoptosis and migration are hallmarks of cancer cells and the main focus of targeted therapies in recent years. The rationale behind targeted therapies is to attack cancer cells without damaging or affecting healthy cells consequently reducing the severe side effect associated with standard chemotherapy. Therefore, a thorough understanding of the underlying cellular pathways leading to proliferation, cell death and metastasis and their alterations in malignant cells is of most importance. In the last 20 years, profilin 1 (Pfn1), a small ubiquitously expressed cytoskeletal protein has been the subject of increased interest as a potential therapeutic target in the fight against several types of cancers including breast, pancreatic, hepatic and bladder cancer. Pfn1 is known to have a reduced expression in these cancer types and increased expression of Pfn1 in some breast cancer cells reduces the tumorigenicity of the cells. It has recently been shown that overexpression of Pfn1 in the human breast cancer cell line MDA-MB 231 induces alterations of the expression of a range of proteins involved in cell proliferation, motility and survival.1 However, the mechanisms underlying the reduced motility and proliferation and increased apoptosis obeserved in these MDA-MB 231 cells are still largely unknown.