STARD3: A Prospective Target for Cancer Therapy

SIMPLE SUMMARY: Alterations in cholesterol level play an important role in cancer development. Lipid transfer proteins (LTPs) are involved in cholesterol distribution between organelles. Among LTPs, some members of steroidogenic acute regulatory-related lipid transfer (START) protein family regulate the cholesterol transportation between organelles and have been revealed as critical for cancer development. This review highlights the recent discoveries of the StAR-related lipid transfer protein domain 3 (STARD3) member of START proteins in cancer development and progression. Blocking cholesterol transportation through the inhibition of STARD3 activity could be an important strategy to treat cancer. ABSTRACT: Cancer is one of the major causes of death in developed countries and current therapies are based on surgery, chemotherapeutic agents, and radiation. To overcome side effects induced by chemo- and radiotherapy, in recent decades, targeted therapies have been proposed in second and even first lines. Targeted drugs act on the essential pathways involved in tumor induction, progression, and metastasis, basically all the hallmark of cancers. Among emerging pathways, the cholesterol metabolic pathway is a strong candidate for this purpose. Cancer cells have an accelerated metabolic rate and require a continuous supply of cholesterol for cell division and membrane renewal. Steroidogenic acute regulatory related lipid transfer (START) proteins are a family of proteins involved in the transfer of lipids and some of them are important in non-vesicular cholesterol transportation within the cell. The alteration of their expression levels is implicated in several diseases, including cancers. In this review, we report the latest discoveries on StAR-related lipid transfer protein domain 3 (STARD3), a member of the START family, which has a potential role in cancer, focusing on the structural and biochemical characteristics and mechanisms that regulate its activity. The role of the STARD3 protein as a molecular target for the development of cancer therapies is also discussed. As STARD3 is a key protein in the cholesterol movement in cancer cells, it is of interest to identify inhibitors able to block its activity.