Pyk2 promotes tumor progression in multiple myeloma

Proline-wealthy tyrosine kinase 2 (Pyk2) is part of the focal adhesion kinase family that’s been lately associated with tumor development. However, its role in modulating multiple myeloma (MM) biology and disease progression remains untouched. We first shown that patients with MM usual to greater expression of Pyk2 in contrast to healthy individuals. By utilizing loss-of-function approaches, we discovered that Pyk2 inhibition brought to decrease in MM tumor development in vivo in addition to decreased cell proliferation, cell-cycle progression, and adhesion ability in vitro. Consequently, overexpression of Pyk2 promoted the malignant phenotype, substantiated by enhanced tumor growth and reduced survival. Mechanistically, inhibition of Pyk2 reduced activation of Wnt/ß-catenin signaling by destabilizing ß-catenin, resulting in downregulation of c-Myc and Cyclin D1. In PND-1186 addition, management of MM cells using the FAK/Pyk2 inhibitor Versus-4718 effectively inhibited MM cell growth in vitro as well as in vivo. With each other, our findings describe the tumor-promoting role of Pyk2 in MM, thus supplying molecular evidence for any novel tyrosine kinase inhibitor like a new therapeutic option in MM.