HGF/c-MET axis contributes to CLL cell survival by regulating multiple mechanisms making it a potential therapeutic target for CLL treatment.

ABSTRACT: Despite significant advances in understanding the occurrence, progression and treatment of chronic lymphocytic leukemia (CLL), there remains a need to explore novel mechanisms and therapeutic strategies. In this study, we discovered that hepatocyte growth factor (HGF), a cytokine highly expressed by bone marrow mesenchymal stem cells within the microenvironment, activates the AKT, ERK and STAT3 signaling pathways, promotes the expression of anti-apoptotic proteins BCL-2, MCL-1, and BCL-xL, thereby enhancing CLL cell survival and resistance to both natural and ABT-199-induced apoptosis. Knockdown of c-MET, the unique receptor for HGF, using lentivirus-mediated shRNA, significantly attenuated the activation of these pro-survival signaling pathways and downregulated the expression of anti-apo

SUBMITTER: Liang S 

PROVIDER: S-EPMC12162569 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature