In the tumor microenvironment, Shh has an autocrine effect initiating cell proliferation and paracrine with the anomalous parenchyma–stromal interaction in OSCC through altered epithelial–mesenchymal transition, involving BMP and BMP receptor families [125,127]; both joined to another redundant mechanism such as Notum potential pro-survival circuit through cross-talking between Shh and Wnt/β-catenin signaling using the via phosphorylation of glycogen synthase kinase-3β [128,129]. The gene discussed is SHH; the disease is neoplasm.