Increasing Ciliary ARL13B Expression Drives Active and Inhibitor-Resistant Smoothened and GLI into Glioma Primary Cilia

ADP-ribosylation factor-like protein 13B (ARL13B), a regulatory GTPase and guanine exchange factor (GEF), enriches in primary cilia promotes tumorigenesis part by regulating Smoothened (SMO), GLI, Sonic Hedgehog (SHH) signaling. Gliomas with increased ARL13B, SMO, GLI2 expression are more aggressive, but the relationship to is unclear. Previous studies have showed that increasing ARL13B glioblastoma cells promoted ciliary SMO accumulation, independent of exogenous SHH addition. Here, we show accumulation due ciliary, not extraciliary, ARL13B. Increasing both activated glioma cilia. ARL13B-driven increases resistant inhibitors, GDC-0449, cyclopamine. Surprisingly, ARL13B-induced changes SMO/GLI2 did correlate canonical downstream pathway genes. However, cell lines whose overexpress WT factor-deficient display reduced INPP5e, membrane component depletion may favor enrichment. Glioma overexpressing also intraflagellar transport 88 (IFT88), suggesting altered retrograde could further promote SMO/GLI accumulation. Collectively, our data suggest factors characteristics IFT proteins, leading drug-resistant GLI. The targets consequences these require investigation.