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Oh, S., Kato, M., Zhang, C., Guo, Y. & Beachy, P. A. A comparison of Ci/Gli activity as regulated by Sufu in Drosophila and mammalian Hedgehog response. PLoS ONE 10, e0135804 (2015). Ermilov, A. N. et al. Maintenance of taste organs is strictly dependent on epithelial hedgehog/GLI signaling. PLoS Genet. 12, e1006442 (2016). This cookie, set by YouTube, registers a unique ID to store data on what videos from YouTube the user has seen. For reasons of hygiene and safety, personal grooming products, cosmetics or items of intimate clothing cannot be returned. Chen, J. K., Taipale, J., Cooper, M. K. & Beachy, P. A. Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev. 16, 2743–2748 (2002).

Pillai, S. G. et al. A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci. PLoS Genet. 5, e1000421 (2009). Aberrant activation of Hh signaling pathway is related to the development of many cancers including basal cell carcinoma (BCC), medulloblastoma (MB) and many solid tumors [ 12, 13]. According to recent studies, PTCH1 mutation is the cause of basal cell nevus syndrome (also known as Gorlin syndrome), which significantly increases the risk of patients with BCC and MB [ 14, 15]. In addition, it has been reported that the inactivation mutation of PTCH1 and the activation mutation of Smo have been found in most spontaneous BCC and MB [ 16, 17]. Given the close relationship between excessive Hh signaling pathway and cancer, numerous researches have been devoted to design and synthesize small molecule inhibitors of Smo for treatment of cancers [ 18, 19, 20]. Oro AE, Higgins K. Hair cycle regulation of Hedgehog signal reception. Dev Biol. 2003;255(2):238–48.Gong, X. et al. Structural basis for the recognition of Sonic Hedgehog by human Patched1. Science https://doi.org/10.1126/science.aas8935 (2018). McLellan, J. S. et al. Structure of a heparin-dependent complex of Hedgehog and Ihog. Proc. Natl Acad. Sci. USA 103, 17208–17213 (2006).

Chen, M. H. et al. Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved. Genes Dev. 23, 1910–1928 (2009). Williams, E. H. et al. Dally-like core protein and its mammalian homologues mediate stimulatory and inhibitory effects on Hedgehog signal response. Proc. Natl Acad. Sci. USA 107, 5869–5874 (2010).Lu, F. Y., Chen, R., Zhou, M. & Guo, Y. Hedgehog signaling modulates cigarette-induced COPD development. Exp. Ther. Med. 22, 729 (2021). Wang J, Mook RA Jr, Lu J, Gooden DM, Ribeiro A, Guo A, et al. Identification of a novel Smoothened antagonist that potently suppresses Hedgehog signaling. Bioorg Med Chem. 2012;20(22):6751–7. Total RNA was extracted from cells using an RNAiso Plus Kit (TaKaRa, Dalian, China) according to the manufacturer's instructions and processed directly to cDNA by reverse transcription with a SuperScript III Kit (TaKaRa, Dalian, China). Semi-quantitative PCR amplification was conducted using Stratagene mx3005p (Agilent). All quantitative PCR amplifications were performed in triplicate with a SYBR Green Kit (TaKaRa, Dalian, China) in an iCycleriQ system (Bio-Rad, Hercules, CA). The mRNA expression level of Gli1 was normalized to that of GUSB. The primers for Gli1 were provided by Invitrogen (Shanghai, China): Gli1: 5′-GCAGTGGGTAACATGAGTGTCT-3′, 5′-AGGCACTAGAGTTGAGGAATTGT-3′. Microscale Thermophoresis (MST) Analysis Yauch, R. L. et al. Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science 326, 572–574 (2009). Ekker, S. C. et al. Patterning activities of vertebrate hedgehog proteins in the developing eye and brain. Curr. Biol. 5, 944–955 (1995).