Hedgehog Signaling Regulates Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem-Like Cells.
Hedgehog Signaling Regulates Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem-Like Cells.
复制标题
Hedgehog 信号传导调节胰腺癌干细胞样细胞的上皮间质转化。
DOI：
10.7150/jca.13305
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发表时间：
2016
影响因子：
3.9
通讯作者：
Yang Y
中科院分区：
文献类型：
--
作者：
Wang F;Ma L;Zhang Z;Liu X;Gao H;Zhuang Y;Yang P;Kornmann M;Tian X;Yang Y
Hedgehog（Hh）信号转导在肿瘤发生中起着至关重要的作用。本研究旨在评估Hh信号在人胰腺癌Panc-1干细胞（CSCs）的上皮-间质转化（EMT）、干细胞特性和化疗耐药性的调节中的作用。用重组慢病毒载体转染Panc-1细胞使SMO沉默，用无血清漂浮培养系统分离Panc-1肿瘤球。采用流式细胞术、实时荧光定量RT-PCR和Western blot检测CSC和EMT标志物的表达。通过成瘤性实验和裸鼠肺转移模型评价Panc-1 CSC的恶性行为。我们发现胰腺癌细胞系Panc-1的肿瘤球具有自我更新、分化和干细胞特性。Hh通路和EMT在Panc-1肿瘤球中活跃。通过SMO敲低抑制Hh信号传导抑制胰腺CSC的自我更新、EMT、侵袭、化学抗性、肺转移、肿瘤发生。结论：Hh信号通路有助于维持胰腺CSC的干细胞样特性和化疗耐药性，促进胰腺癌的发生和转移。Hh通路是胰腺肿瘤干细胞治疗策略的潜在靶点。
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.