SMAD4 Regulates the Expression of LCK Affecting Chimeric Antigen Receptor-T Cells Proliferation Through PI3K/Akt Signaling Pathway.

ABSTRACT: The proliferation of CAR-T cells was hindered and cannot play its killing function well in solid tumors. And yet the regulatory mechanism of CAR-T cell proliferation is not fully understood. Here, we showed that recombinant expression of CD19CAR in T cells significantly increased the basal activation level of CAR-T cells and LCK activation. Both LCK and SMAD4 were essential for CAR-T cells proliferation since over-express LCK or SMAD4 significantly promotes CAR-T cells proliferation, while knock-down LCK or SMAD4 expression inhibited the proliferation of CAR-T cells seriously. More cells go into apoptosis when knock-down LCK or SMAD4 expression, and the cell cycle was arrested in G2/M or S phase, respectively. Over-express LCK or SMAD4 significantly promotes phosphorylation of PI3K and Akt

SUBMITTER: Wan R 

PROVIDER: S-EPMC11704455 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature