Title | Hedgehog Signaling Regulates Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem-Like Cells |
Authors | Wang, Feng Ma, Ling Zhang, Zhengkui Liu, Xiaoran Gao, Hongqiao Zhuang, Yan Yang, Pei Kornmann, Marko Tian, Xiaodong Yang, Yinmo |
Affiliation | Peking Univ, Hosp 1, Dept Gen Surg, 8th Xishiku St, Beijing 100034, Peoples R China. Purdue Univ, Dept Agr & Biol Engn, W Lafayette, IN 47906 USA. Univ Ulm, Clin Gen Visceral & Transplantat Surg, D-89081 Ulm, Germany. Peking Univ, Canc Hosp & Inst, Dept Breast Oncol, Beijing 100142, Peoples R China. |
Keywords | Hedgehog pancreatic cancer cancer stem cell epithelial-mesenchymal transition IDENTIFICATION PROPAGATION CULTURE PATHWAY |
Issue Date | 2016 |
Publisher | JOURNAL OF CANCER |
Citation | JOURNAL OF CANCER.2016,7,(4),408-417. |
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. |
URI | http://hdl.handle.net/20.500.11897/434737 |
ISSN | 1837-9664 |
DOI | 10.7150/jca.13305 |
Indexed | SCI(E) PubMed |
Appears in Collections: | 第一医院 北京肿瘤医院 |