J Cancer 2016; 7(4):408-417. doi:10.7150/jca.13305

Research Paper

Hedgehog Signaling Regulates Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem-Like Cells

Feng Wang1, Ling Ma1, Zhengkui Zhang1, Xiaoran Liu4, Hongqiao Gao1, Yan Zhuang1, Pei Yang2, Marko Kornmann3, Xiaodong Tian1, ✉, Yinmo Yang1,✉

1. Department of General Surgery, Peking University First Hospital, Beijing 100034, People's Republic of China
2. Department of Agricultural & Biological Engineering, Purdue University, West Lafayette, IN 47906, USA
3. Clinic of General, Visceral and Transplantation Surgery, University of Ulm, Ulm 89081, Germany
4. Department of Breast Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China

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.

Keywords: Hedgehog, pancreatic cancer, cancer stem cell, epithelial-mesenchymal transition

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How to cite this article:
Wang F, Ma L, Zhang Z, Liu X, Gao H, Zhuang Y, Yang P, Kornmann M, Tian X, Yang Y. Hedgehog Signaling Regulates Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem-Like Cells. J Cancer 2016; 7(4):408-417. doi:10.7150/jca.13305. Available from http://www.jcancer.org/v07p0408.htm