Hedgehog pathway and cancer: A new area (Review)

Abstract

In years of research on classical pathways, the composition, information transmission mechanism, crosstalk with other pathways, and physiological and pathological effects of hedgehog (HH) pathway have been gradually clarified. HH also plays a critical role in tumor formation and development. According to the update of interpretation of tumor phenotypes, the latest relevant studies have been sorted out, to explore the specific mechanism of HH pathway in regulating different tumor phenotypes through gene mutation and signal regulation. The drugs and natural ingredients involved in regulating HH pathway were also reviewed; five approved drugs and drugs under research exert efficacy by blocking HH pathway, and at least 22 natural components have potential to treat tumors by HH pathway. Nevertheless, there is a deficiency of existing studies. The present review confirmed the great potential of HH pathway in future cancer treatment with factual basis.

Keywords: cancer; hedgehog; phenotype; signaling pathway.

Figure 1.

Classical HH pathway. Activation of the classical HH pathway is dependent on HH ligands, which can be bind to and then internalize PTCH, relieving the inhibition of SMO on the intracellular vesicles, and transmit HH signal to SUFU. Thus, GliFL receives relevant signals to form Gli-A and promotes the transcription process of HH target genes. HH, Hedgehog; PTCH, Patched; SMO, Smoothened; SUFU, suppressor of fused protein; Gli-A, GLI, family zinc finger 1; IHH, Indian HH; DHH, dessert HH; PKA, protein kinase CAMP-activated catalytic subunit alpha; CK1, casein kinase 1 alpha 1; GSK-3β, glycogen synthase kinase 3 beta; b-TrCP, beta-transducin repeat containing E3 ubiquitin protein ligase; Kif7, kinesin family member 7; FOXA2, forkhead box A2; HIP, collagen type II alpha 1 chain.

Figure 2.

Influences of HH pathway on cancer phenotype. Information interaction between tumor cells and tumor stromal cells can be realized via HH pathway. This eventually regulates genome instability mutation, non-mutational epigenetic reprogramming, tumor promoting inflammation, immune destruction, senescent cells, invasion and metastasis, accessing vasculature, and cellular metabolism. HH, Hedgehog; PTCH, patched; SMO, smoothened; SUFU, suppressor of fused protein.