title: SDF-1/CXCR4 signaling induces pancreatic cancer cell invasion and epithelial-mesenchymal transition in vitro through non-canonical activation of Hedgehog pathway.
abstract: In our previous study, we found that blockade of SDF-1/CXCR4 signaling inhibits pancreatic cancer cell migration and invasion in vitro. However, the mechanism governing the downstream regulation of SDF-1/CXCR4-mediated invasion remains unclear. Here we report the role of SDF-1/CXCR4 in pancreatic cancer and the possible mechanism of SDF-1/CXCR4-mediated pancreatic cancer invasion. We show that there is a cross-talk between SDF-1/CXCR4 axis and non-canonical Hedgehog (Hh) pathway in pancreatic cancer. Furthermore, our data demonstrate that the ligand of CXCR4, SDF-1 induces CXCR4-positive pancreatic cancer invasion, epithelial-mesenchymal transition (EMT) process and activates the non-canonical Hh pathway. Moreover, we also demonstrate that the invasion of a pancreatic cancer and EMT resulting from the activation of SDF-1/CXCR4 axis is effectively inhibited by Smoothened (SMO) inhibitor cyclopamine and siRNA specific to Gli-1. Collectively, these data demonstrate that SDF-1/CXCR4 modulates the non-canonical Hh pathway by increasing the transcription of SMO in a ligand-independent manner. Taken together, SDF-1/CXCR4 axis may represent a promising therapeutic target to prevent pancreatic cancer progression.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Shaanxi, China.
authors.forename: Xuqi
authors.initials: X
authors.lastname: Li
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Ma
authors.forename: Qinhong
authors.initials: Q
authors.lastname: Xu
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Lei
authors.forename: Wanxing
authors.initials: W
authors.lastname: Duan
authors.forename: Kruttika
authors.initials: K
authors.lastname: Bhat
authors.forename: Fengfei
authors.initials: F
authors.lastname: Wang
authors.forename: Erxi
authors.initials: E
authors.lastname: Wu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D053823:Hedgehog Proteins; D019718:Receptors, CXCR4; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor