Dual roles of FAK in tumor angiogenesis: A review focused on pericyte FAK

Abstract

Focal adhesion kinase (FAK), also known as protein tyrosine kinase 2 (PTK2), is a ubiquitously expressed non-receptor tyrosine kinase, that plays a pivotal role in integrin-mediated signal transduction. Endothelial FAK is upregulated in many types of cancer and promotes tumorigenesis and tumor progression. However, recent studies have shown that pericyte FAK has the opposite effect. This review article dissects the mechanisms, by which endothelial cells (ECs) and pericyte FAK regulate angiogenesis, with an emphasis on the Gas6/Axl pathway. In particular, this article discusses the role of pericyte FAK loss on angiogenesis during tumorigenesis and metastasis. In addition, the existing challenges and future application of drug-based anti-FAK targeted therapies will be discussed to provide a theoretical basis for further development and use of FAK inhibitors.

Keywords: FAK; FAK inhibitors; Pericyte; Tumor angiogenesis; Vasculogenic mimicry.