SMO and cancer: Prostate cancer (PCa) is the second most common cancer in male accounting for 14.1% new cases worldwide.185 Paracrine signaling of HH signaling pathway is crucial to prostate development.234 PCa originates from prostatic epithelia and epithelial-mesenchymal interaction plays an important role in PCa progression and metastasis.256,257 Wilkinson et al. has shown the co-localization of Smo with primary cilia in prostatic fibroblasts and confirmed the activated HH signaling pathway in prostatic tumor microenvironment.258 Also, Shh expression level was correlated with cell proliferation in PCa.