Role of Pyk2 in Human Cancers

Abstract

Proline-rich tyrosine kinase 2 (Pyk2) plays essential roles in tumorigenesis and tumor progression. Pyk2 serves as a non-receptor tyrosine kinase regulating tumor cell survival, proliferation, migration, invasion, metastasis, and chemo-resistance, and is associated with poor prognosis and shortened survival in various cancer types. Thus, Pyk2 has been traditionally regarded as an oncogene and potential therapeutic target for cancers. However, a few studies have also demonstrated that Pyk2 exerts tumor-suppressive effects in some cancers, and anti-cancer treatment of Pyk2 inhibitors may only achieve marginal benefits in these cancers. Therefore, more detailed knowledge of the contradictory functions of Pyk2 is needed. In this review, we summarized the tissue distribution, expression, interactive molecules of Pyk2 in the signaling pathway, and roles of Pyk2 in cancers, and focused on regulation of the interconnectivity between Pyk2 and its downstream targets. The potential use of inhibitors of Pyk2 and its related pathways in cancer therapy is also discussed.

Figure 1

Schematic model of Pyk2 functional domains correlated with tumor progression. Pyk2 contains an N-terminal FERM domain, a central kinase domain, and a C-terminal focal adhesion targeting (FAT) domain. The phosphorylation sites Tyr402, Tyr579, Tyr580, and Tyr881 also take part in regulating the growth of tumor cells. Additionally, Pyk2 includes 3 proline-rich regions located among the structure domains of Pyk2.

Figure 2

Schematic model of the suppressive role of Pyk2 in prostate cancer progression. Black arrows indicate a promoting effect and red arrows indicate an inhibiting effect. The activation of Pyk2 inhibits cancer progression in androgen-dependent prostate cancer.

Figure 3

Schematic model of the suppressor role of Pyk2 in neuroblastoma progression. Black arrows show the promoting effect and red arrows show the inhibiting effect. The activation of Pyk2 leads to neuroblastoma cell death. Regulation of Pyk2 phosphorylation can affect neuroblastoma progression.