title: Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation             and metastasis.
abstract: Pancreatic cancer is one of the most aggressive and devastating malignancies.             The Hedgehog (Hh) pathway has been reported to play an important role in pancreatic             cancer development and progression. The aim of this study was to examine the activation             of the Hh pathway in human pancreatic cancer tissue samples and pancreatic cancer             cell lines, and the molecular mechanisms involved in the Hh pathway mediated effects             on pancreatic cancer cell proliferation and invasion. The expression levels of             Hh molecules in human pancreatic cancer tissue samples and pancreatic cancer cell             lines were evaluated using RT-PCR. The role of the Hh pathway in cell proliferation             and invasion was evaluated using flow cytometry, MTT, colony formation assays             and transwell invasion assays, and the expression of cancer stem cell markers             and epithelial-mesenchymal transition (EMT) were evaluated using flow cytometry             and RT-PCR. Tumorigenicity assays were used to further investigate the role of             the Hh pathway in vivo. Hh molecules were highly expressed in human pancreatic             cancer tissue samples and pancreatic cancer cell lines. Inhibition of the Hh pathway             notably decreased cell proliferation and induced apoptosis through inhibition             of the PI3K/AKT pathway and cancer stem cells. Furthermore, inhibition of the             Hh signaling pathway significantly inhibited EMT by suppressing the activation             of transcription factors Snail and Slug, which are correlated with significantly             reduced pancreatic cancer cell invasion, suggesting that the Hh signaling pathway             is involved in early metastasis. These results indicate that activation of the             Hh pathway is a common event. Inhibition of the Hh pathway may be a potential             molecular target of new therapeutic strategies for pancreatic cancer.
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Hao
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Tian
authors.forename: Chang-Fu
authors.initials: CF
authors.lastname: Qin
authors.forename: Xue-Hai
authors.initials: XH
authors.lastname: Xie
authors.forename: Yin-Mo
authors.initials: YM
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism; D055785:Gene Knockdown Techniques; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D013357:Subgingival Curettage; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt