Pyk2 silencing decreases MM tumor growth in a mouse xenograft model. (A) Inhibition of Pyk2 induced by shRNA (A2 and A4) in GFP⁺/Luc⁺-MM.1S cells was validated using qPCR. No compensatory increase of FAK was observed. (B) shRNA-mediated FAK inhibition in GFP⁺/Luc⁺-MM.1S cells did not induce a compensatory increase of Pyk2. (C-D) SCID/Beige mice were injected IV with GFP⁺/Luc⁺-MM.1S Pyk2-knockdown (A4) or FAK-knockdown cells (3 × 10⁶/ mouse) to establish an MM xenograft model (n = 5 per group). Tumor burden was detected and quantified using BLI. Inhibition of Pyk2 significantly reduced MM tumor burden compared with scramble control. Quantification of tumor burden has been detected by BLI (bars indicate mean ± SD; P indicates P values). (E) Mice bearing Pyk2-knockdown cells exhibited significantly prolonged survival (P < .0001), whereas inhibition of FAK did not prolong the survival of mice. (F) Inhibition of Pyk2 in CD138⁺ tumor cells derived from BM of Pyk2-knockdown mice was reconfirmed by immunohistochemistry. K.D., knockdown; n.s., not significant; scr, scramble control.