Overexpression of Pyk2 enhances MM cell proliferation, adhesion, and cell-cycle progression. (A) GFP⁺/Luc⁺-MM.1S Pyk2-overexpressing cells were cultured alone or in the presence of MM-BMSCs for 48 hours. Overexpression of Pyk2 increased MM cell proliferation in the presence or absence of MM-BMSCs. (B) Overexpression of Pyk2 promotes MM cell-cycle progression by increasing the G2/M phase population. (C-D) GFP⁺/Luc⁺-MM.1S Pyk2-overexpressing cells were cultured in MM-BMSC–coated or fibronectin-coated wells for 2 hours. Overexpression of Pyk2 enhanced the adhesion ability of MM cells to BMSCs (P = .0017) and fibronectin (P = .0021). (E) Overexpression of Pyk2 increased β-catenin, c-Myc, and Cyclin D1 expression. (F) Increased mRNA levels of Pyk2, β-catenin, and c-Myc in BM specimens harvested from mice that were injected with Pyk2-overexpressing cells. (G) Overexpression of Pyk2 further enhanced the upregulation and nuclear translocation of β-catenin in MM cells induced by interaction with BMSCs, resulting in higher nuclear c-Myc expression. (H) Src and Paxillin were activated upon increased activity of Pyk2.