Dual PAK4-NAMPT Inhibition Impacts Growth and Survival, and Increases Sensitivity to DNA-Damaging Agents in Waldenstrom Macroglobulinemia.

ABSTRACT:

Purpose

p21-activated kinase 4 (PAK4) plays a significant biological and functional role in a number of malignancies, including multiple myeloma (MM). On the basis of our promising findings in MM, we here characterize PAK4 expression and role in WM cells, as well effect of dual PAK4-NAMPT inhibitor (KPT-9274) against WM cell growth and viability.

Experimental design

We have analyzed mRNA and protein expression levels of PAK4 in WM cells, and used loss-of-function approach to investigate its contribution to WM cell viability. We have further tested the in vitro and in vivo effect of KPT-9274 against WM cell growth and viability.

Results

We report here high-level expression and functional role of PAK4 in WM, as demonstrated by shRNA-mediated knockdown; and

SUBMITTER: Li N 

PROVIDER: S-EPMC6320280 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature