FHL1 promotes glioblastoma aggressiveness through regulating EGFR expression.

The four and a half LIM domains protein 1 (FHL1) plays a key role in multiple cancers. Here, we characterized its role in glioblastoma, the most common and incurable form of brain cancer. Overexpression of FHL1 promotes growth, migration, and invasion of glioblastoma cells in vivo and in vitro. In contrast, FHL1 silencing by RNAi exhibits the opposite effects. FHL1 interacts with the transcription factor SP1 to upregulate EGFR expression and activate the downstream signaling cascades, including Src, Akt, Erk1/2, and Stat3, leading to glioblastoma malignancy. FHL1 is highly expressed and positively correlated with EGFR levels in human glioblastoma, particularly those of the classical subtype. Our results suggest that the FHL1-SP1-EGFR axis plays a tumor-promoting role and highlight the translational potential of inhibiting FHL1 for glioblastoma treatment.