Sohlh1 suppresses glioblastoma cell proliferation, migration, and invasion by inhibition of Wnt/β-catenin signaling.

Glioblastoma (GBM) is the most aggressive and highly invasive type of astrocytic tumors. Despite advances in diagnosis and therapy, the prognosis and survival time remain poor. Identifying key mediators of tumor cell proliferation, migration, and invasion is crucial to the development of new and more effective therapies. In this paper, we report the novel role of Spermatogenesis- and oogenesis- specific basic helix-loop-helix transcription factor1 (Sohlh1) in the inhibition of Wnt/β-catenin signaling and aggressive behaviors in GBM cells. Immunohistochemistry was performed to examine the expression of Sohlh1 and related proteins in astrocytomas. Human glioblastoma U87 and U251 cellswere transfected with appropriate plasmids and/or siRNAs to evaluate their functions on cell proliferation, migration, and invasion. Western blot and TOPflash luciferase assay were used to determine the involvement of Wnt/β-catenin signaling pathway in Sohlh1-mediated cellular activities in glioblastomas. We observed that Sohlh1 was downregulated in astrocytomas. The reduction in Sohlh1 expression was inversely correlated with the degree of malignancy in astrocytomas. In GBM cell lines, cellular proliferation, migration, and invasion were significantly enhanced after Sohlh1 knockdown, but significantly inhibited after Sohlh1 overexpression. These functional effects of Sohlh1 were achieved by upregulating GSK3β and inhibiting Wnt/β-catenin signaling. Our findings provide novel mechanistic insights of Sohlh1 in malignant progression of astrocytomas, suggesting that the level of Sohlh1 expression may be a predictor of astrocytoma behavior and further, Sohlh1 may serve as a potential therapeutic target for GBM.