HIPK2 in cancer biology and therapy: Recent findings and future perspectives

Homeodomain-interacting protein kinase 2 (HIPK2) is a serine-threonine kinase that phosphorylates and regulates a plethora of transcriptional regulators and chromatin modifiers. The heterogeneity of its interactome allows HIPK2 to modulate several cellular processes and signaling pathways, ultimately regulating cell fate and proliferation. Because of its p53-dependent pro-apoptotic activity and its downregulation in many tumor types, HIPK2 is traditionally considered a bone fide tumor suppressor gene. However, recent findings revealed that the role of HIPK2 in the pathogenesis of cancer is much more complex, ranging from tumor suppressive to oncogenic, strongly depending on the cellular context. Here, we review the very recent data emerged in the last years about the involvement of HIPK2 in cancer biology and therapy, highlighting the various alterations of this kinase (downregulation, upregulation, mutations and/or delocalization) in dependence on the cancer types. In addition, we discuss the recent advancement in the understanding the tumor suppressive and oncogenic functions of HIPK2, its role in establishing the response to cancer therapies, and its regulation by cancer-associated microRNAs. All these data strengthen the idea that HIPK2 is a key player in many types of cancer; therefore, it could represent an important prognostic marker, a factor to predict therapy response, and even a therapeutic target itself.

Automated summary

Homeodomain-interacting protein kinase 2 (HIPK2) is a versatile enzyme involved in the phosphorylation and regulation of transcriptional regulators and chromatin modifiers. Recent research has shown that HIPK2 has a complex role in cancer, with both tumor suppressive and oncogenic functions depending on the cellular context. This review summarizes the latest data on the involvement of HIPK2 in cancer biology and therapy, highlighting the alterations of this kinase in different cancer types. HIPK2 is emerging as a key player in cancer and could potentially serve as a prognostic marker, a predictor of therapy response, and a therapeutic target.