Wnt5a induces ROR1 dependent NF-κB activation to enhance MMP-9 expression and invasiveness in chronic lymphocytic leukemia.

ABSTRACT: Matrix metalloproteinase-9 (MMP-9) facilitates the extravasation and lymphoid-tissue infiltration of chronic lymphocytic leukemia (CLL) cells. Prior studies found that high level expression of MMP-9 in CLL associates more aggressive disease. We find that circulating CLL cells that express high levels the onco-embryonic protein ROR1 express significantly higher levels of MMP-9. Stimulation of CLL cells with Wnt5a could enhance expression and the release of MMP-9 into the culture media and increase the capacity of CLL cells to invade Matrigel in a Boyden-Chamber Assay. Such effects of Wnt5a could not be inhibited by BTK inhibitors such as ibrutinib or zanubrutinib, but could be blocked by zilovertamab, a humanized mAb specific for ROR1. We found that siRNA silencing of NF-κB-p65 or use of an

SUBMITTER: Hasan MK 

PROVIDER: S-EPMC12208867 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature