C3G deregulation uncovers a dual role in B-cell lymphoma: tumor suppression and enhanced metastasis via Rap1 and Rac2 signaling.

ABSTRACT:

Background

C3G (RapGEF1) is a guanine nucleotide exchange factor that activates Rap1, a small GTPase implicated in hematologic malignancies. We previously showed that C3G GEF activity is self-repressed via its AIR (autoinhibitory region). A lymphoma-associated missense mutation (Y554H) disrupts this inhibition, resulting in constitutive activation. This study aims to investigate the consequences of C3G dysregulation in B-cell lymphoma.

Methods

Murine C3G mutation Y564H (equivalent to human Y554H) was introduced into the A20 B-cell lymphoma line using CRISPR/Cas9. Rap1 activation, proliferation, apoptosis, ERK1/2 phosphorylation, Rac2 activity, adhesion, migration, invasion, tumorigenicity, and transcriptomic changes were assessed through biochemical assays, in vitro function

SUBMITTER: Moran-Vaquero A 

PROVIDER: S-EPMC12781495 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature