The Hedgehog (Hh) signaling pathway is essential to the development of tissues and organs. Hyperactive Hh signaling has been implicated in many gastric cancers, including esophageal cancer. However, the interaction between the Hh pathway and other potential signaling pathways in primary esophageal tumorigenesis has not been well investigated. In this study, we found that esophageal cancer cells expressed Hh signaling molecules and that the hyperexpression of Hh target genes was related to AKT but not ERK activation. We analyzed the relationship between Gli1 or p-AKT expression and clinicopathological features in esophageal carcinoma samples and found that Gli1 expression was associated with lymph vessel invasion (p = 0.016), blood vessel invasion (p = 0.006) and a poor prognosis (p = 0.003), and p-AKT expression was associated with blood vessel invasion (p = 0.031) and a poor prognosis (p = 0.031). We also studied the relationship between Hh and PI3K/AKT or MAPK signaling pathways in both TE-1 and TE-10 cell lines. We found that the PI3K/AKT pathway played a critical role in Hh signaling after stimulation with EGF, Gβγ and N-Shh. Conversely, PI3K/AKT and MAPK signaling cooperated with the Shh pathway to promote esophageal cancer cell survival and proliferation. The results from esophageal cancer cells shed light on the significance of Hh signaling in esophageal tumor formation and the crosstalk of the Hh pathway with other basic signaling pathways, which is consistent with that observed in human tumor samples.

PMID: 20839260 [PubMed - as supplied by publisher] Source: National Library of Medicine.