CCDC50 promotes glioblastoma progression through regulating EGFR cell-surface recycle
Glioblastomas (GBM) are a kind of malignant tumor with high mortality. However, the mechanism of tumor progression remains poorly understood. Specifically, we find that the expression of autolysosome-associated protein CCDC50, is positively correlated with tumor malignancy, and poor survival of GBM patients. CCDC50 functions as a specific cargo adaptor to assist EGFR recycling back to the plasma membrane, leading to prolonged activation of the downstream signaling pathways. We reveal that targeting CCDC50 in GBM may be a promising therapeutic strategy, as CCDC50 deficiency significantly inhibited the proliferation and migration of tumor cells in vitro and in vivo. Moreover, targeting CCDC50 together with alkylating agent temozolomide (TMZ) induces synergistic function in regression of GBM tumors, representing an alternative strategy for malignant tumor therapy. We performed transcriptome profiling (RNA-seq) and quantitative reverse transcription polymerase chain reaction (qRT–PCR) in shCtrl and shCCDC50 cells to evaluate the GBM tumor growth and metastasis controlled by CCDC50. Overall design: U87 cells were transduced with lentivirus carring shCtrl or shCCDC50 plasmids. The infected cells were selected with puromycin for 7 days. The deletion of CCDC50 was confirmed by qRT-PCR and immunobloting. The shCtrl and shCCDC50 cells were collected for mRNA profilling analysis.