ECE1c promotes glioblastoma invasion via the ROCK2-MYH10 axis and interaction with ACTB

Glioblastoma is the most malignant primary intracranial tumor and is characterized by rapid growth, diffuse invasion, and notable therapeutic resistance. The mesenchymal subtype of glioblastoma multiforme (GBM) is the most aggressive, but the underlying regulatory network of this phenotype has not yet been fully elucidated.

Bioinformatic analysis was performed to identify the heterogeneity of ECE1 expression and its prognostic roles. Cytological experiments were conducted to evaluate the function of ECE1 in GBM cell lines. Tumor xenograft models were established to access intracranial GBM growth in vivo. Protein interactions and signaling mechanisms were investigated by coimmunoprecipitation, immunofluorescence, and Western blot.

In the present study, our analyses revealed that ECE1 is closely associated with the mesenchymal subtype, CD44 expression, and prognosis of GBM. We found that ECE1c was the most common isoform in GBM. The knockdown of ECE1 reduced both the proliferation and invasiveness of GBM cells, whereas overexpression of ECE1c promoted tumor malignancy. Mechanistic studies revealed that ECE1c activates the ROCK2 signaling pathway and interacts with ACTB, thereby modulating cytoskeletal remodeling and promoting pseudopodia formation, which together increase the invasive capacity of GBM.

Our results indicate that ECE1c is a key regulator of GBM invasion through ROCK2 activation and interaction with ACTB. Targeting ECE1c may represent a viable therapeutic strategy for treating invasive GBM.