The role of the HH signaling pathway in lung cancer. (a) The HH signaling pathway in SCLC. The autocrine HH signaling pathway promotes cancer cell proliferation. (b) The HH signaling pathway in adenocarcinoma. The noncanonical GLI activation pathway would maintain cancer cell proliferation. CAF maintenance would be regulated by paracrine HH signaling pathway activation. CAF-secreted HH ligands would activate the HH signaling pathway in cancer cells and CSCs. CAFs-mediated paracrine HH pathway activation in cancer cells has important roles in acquisition of metastatic properties. Moreover, CAF-mediated HH signaling pathway activation might be involved in CSC maintenance. Cancer cells harboring metastatic properties and CSCs would be also maintained by autocrine HH signaling pathway activation. In addition, SMO might activate other signaling molecules in cancer cells harboring metastatic properties. (c) The HH signaling pathway in LSCC. Cancer cells would be maintained by the noncanonical GLI2 activation pathway. PRKCI-SOX2-HH signaling pathway has important roles in CSC maintenance.