期刊
FEBS LETTERS
卷 595, 期 1, 页码 85-98出版社
WILEY
DOI: 10.1002/1873-3468.13955
关键词
EGFR; FHL1; glioblastoma; SP1
资金
- Suzhou 'Science and Education for Health' Youth Science and Technology Project [KJXW2018013]
- Second Affiliated Hospital of Soochow University Youth pre-Research Fund [SDFEYQN1716]
- National Natural Science Foundation of China [81572480, 81172401]
The FHL1 protein promotes tumor growth and invasion in glioblastoma by interacting with EGFR and SP1, affecting the signaling cascades in GBM cells.
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.
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