title: Hedgehog Signaling Regulates Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem-Like Cells.
abstract: Hedgehog (Hh) signaling is crucially involved in tumorigenesis. This study aimed to assess the role of Hh signaling in the regulation of epithelial-mesenchymal transition (EMT), stemness properties and chemoresistance of human pancreatic Panc-1 cancer stem cells (CSCs). Panc-1 cells were transfected with recombinant lentiviral vectors to silence SMO and serum-free floating-culture system was used to isolate Panc-1 tumorspheres. The expression of CSC and EMT markers was detected by flow cytometry, real-time RT-PCR and Western blot analysis. Malignant behaviors of Panc-1 CSC were evaluated by tumorigenicity assays and nude mouse lung metastasis model. We found that tumorspheres derived from pancreatic cancer cell line Panc-1 possessed self-renewal, differentiation and stemness properties. Hh pathway and EMT were active in Panc-1 tumorspheres. Inhibition of Hh signaling by SMO knockdown inhibited self-renewal, EMT, invasion, chemoresistance, pulmonary metastasis, tumorigenesis of pancreatic CSCs. In conclusion, Hh signaling contributes to the maintenance of stem-like properties and chemoresistance of pancreatic CSC and promotes the tumorigenesis and metastasis of pancreatic cancer. Hh pathway is a potential molecular target for the development of therapeutic strategies for pancreatic CSCs.
authors.affiliation: 1. Department of General Surgery, Peking University First Hospital, Beijing 100034, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: 1. Department of General Surgery, Peking University First Hospital, Beijing 100034, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ma
authors.affiliation: 1. Department of General Surgery, Peking University First Hospital, Beijing 100034, People's Republic of China.
authors.forename: Zhengkui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 4. Department of Breast Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Liu
authors.affiliation: 1. Department of General Surgery, Peking University First Hospital, Beijing 100034, People's Republic of China.
authors.forename: Hongqiao
authors.initials: H
authors.lastname: Gao
authors.affiliation: 1. Department of General Surgery, Peking University First Hospital, Beijing 100034, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhuang
authors.affiliation: 2. Department of Agricultural & Biological Engineering, Purdue University, West Lafayette, IN 47906, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Yang
authors.affiliation: 3. Clinic of General, Visceral and Transplantation Surgery, University of Ulm, Ulm 89081, Germany.
authors.forename: Marko
authors.initials: M
authors.lastname: Kornmann
authors.affiliation: 1. Department of General Surgery, Peking University First Hospital, Beijing 100034, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Tian
authors.affiliation: 1. Department of General Surgery, Peking University First Hospital, Beijing 100034, People's Republic of China.
authors.forename: Yinmo
authors.initials: Y
authors.lastname: Yang
keywords: Hedgehog; cancer stem cell; epithelial-mesenchymal transition; pancreatic cancer