Recombinant Shh protein enhanced cell proliferation and suppressed the expression of E-cadherin in RCC cell lines, suggesting the essential role of EMT modulating by HH signaling pathway in RCC.253 HH signaling pathway may interact with hypoxia-inducible factor 2α modulating the radiosensitivity of RCC.254 Furukawa et al. suggested that Gli2 may be related to the underlying mechanism of drug resistance associated with tyrosine kinase inhibitor (TKI) inhibitors sunitinib in CRCC.255. The gene discussed is SHH; the disease is renal cell carcinoma.