HIPK2 in Angiogenesis: A Promising Biomarker in Cancer Progression and in Angiogenic Diseases

SIMPLE SUMMARY: Dysregulated angiogenesis contributes to cancer progression and to many chronic inflammatory diseases. Many efforts in the field of angiogenesis have been made to discover new potential molecular targets to be used as biomarkers or to improve the anti-angiogenic therapies. HIPK2, an oncosuppressor able to regulate multiple molecular pathways, has been shown lately to play a role in angiogenesis both in cancer and in other angiogenic diseases. Therefore, HIPK2 emerges as a potential new biomarker of angiogenic diseases. ABSTRACT: Angiogenesis is the formation of new blood capillaries taking place from preexisting functional vessels, a process that allows cells to cope with shortage of nutrients and low oxygen availability. Angiogenesis may be activated in several pathological diseases, from tumor growth and metastases formation to ischemic and inflammatory diseases. New insights into the mechanisms that regulate angiogenesis have been discovered in the last years, leading to the discovery of new therapeutic opportunities. However, in the case of cancer, their success may be limited by the occurrence of drug resistance, meaning that the road to optimize such treatments is still long. Homeodomain-interacting protein kinase 2 (HIPK2), a multifaceted protein that regulates different molecular pathways, is involved in the negative regulation of cancer growth, and may be considered a “bona fide” oncosuppressor molecule. In this review, we will discuss the emerging link between HIPK2 and angiogenesis and how the control of angiogenesis by HIPK2 impinges in the pathogenesis of several diseases, including cancer.