Tumor suppressor cylindromatosis (CYLD) dysfunction by its downregulation is significantly associated with poor prognosis in patients with glioblastoma (GBM), the most aggressive and malignant type of glioma. However, no effective treatment is currently available for patients with CYLD‑downregulated GBM. The aim of the present study was to identify the crucial cell signaling pathways and novel therapeutic targets for CYLD downregulation in GBM cells. CYLD knockdown in GBM cells induced GBM malignant characteristics, such as proliferation, metastasis, and GBM stem‑like cell (GSC) formation. Comprehensive proteomic analysis and RNA sequencing data from the tissues of patients with GBM revealed that Wnt/β‑catenin signaling was significantly activated by CYLD knockdown in patients with GBM. Furthermore, a Wnt/β‑catenin signaling inhibitor suppressed all CYLD knockdown‑induced malignant characteristics of GBM. Taken together, the results of the present study revealed that Wnt/β‑catenin signaling is responsible for CYLD silencing‑induced GBM malignancy; therefore, targeting Wnt/β‑catenin may be effective for the treatment of CYLD‑negative patients with GBM with poor prognosis.
Keywords: CYLD; GBM stem‑like cells; Wnt/β‑catenin signaling; glioblastoma.