The four-and-a-half LIM domain protein 1 (FHL1) plays a key role in multiple cancers. Here, we characterized its role in glioblastoma (GBM), the most common and incurable form of brain cancer. Overexpression of FHL1 promotes growth, migration, and invasion of GBM 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 epidermal growth factor receptor (EGFR) expression and activate the downstream signaling cascades, including Src, Akt, Erk1/2, and Stat3, leading to GBM malignancy. FHL1 is highly expressed and positively correlated with EGFR levels in human GBM, 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 GBM treatment.
Bibliographical noteFunding Information:
This work was supported by grants from the Suzhou ‘Science and Education for Health’ Youth Science and Technology Project (KJXW2018013, to SL) and the Second Affiliated Hospital of Soochow University Youth pre‐Research Fund (SDFEYQN1716, to CL). This work was also supported by the grant from the National Natural Science Foundation of China (81572480 and 81172401).
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