Filamin A as a key regulator of the tumor suppressor Deleted in liver cancer 1 (DLC1)

We identify a previously unknown interaction between the tumor suppressor DLC1 and Filamin A. Filamin A acts as a dual regulator of the RhoA-MRTF-A/SRF signaling axis, promoting gene transcription via MRTF-A or activating DLC1 to suppress transcription and induce senescence. This balance is controlled by phosphorylation of Filamin A at serine 2152, which determines whether Filamin A binds to DLC1 or MRTF-A. In hepatocellular carcinoma mouse models, high levels of phosphorylated FLNA correlate with reduced DLC1 expression. These findings highlight FLNA phosphorylation as a potential biomarker and therapeutic target, thereby providing new mechanistic insight into DLC1 downregulation in liver cancer.