Liu Qingfeng, Sheng Weiwei, Dong Ming, Dong Xiaoshen, Dong Qi, Li Feng
Department of General Surgery, Gastrointestinal Surgery, the First Hospital, China Medical University, Shenyang, China; Department of General Surgery, the People's Hospital of Liaoning Province, Shenyang, China.
Department of General Surgery, Gastrointestinal Surgery, the First Hospital, China Medical University, Shenyang, China.
Surgery. 2015 Jul;158(1):211-24. doi: 10.1016/j.surg.2015.03.016.
The Hedgehog signaling pathway and its key target effector Gli1 are linked closely to the development of the epithelial to mesenchymal transition (EMT) in many cancers. The definite function of Gli1 in regulating the EMT of pancreatic cancer (PC), however, is still unclear.
At the cell and tissue levels, we investigated the role of Gli1 in the initiation of EMT in PC with and without external stimulus treatments.
The immunohistochemistry results showed that Gli1 was associated positively with MMP9 but not with E-cad or Vimentin. Gli1 expression was associated positively with tumor T (P = .025) and Union for International Cancer Control stage (P = .032), whereas MMP9 expression was associated positively with lymph node metastasis (P = .017) and Union for International Cancer Control stage (P = .006). Furthermore, patients with Gli1 and MMP9 coexpression had poor overall survival (P = .015). Silencing of Gli1 alone without external stimulus had no effect on EMT but inhibited transforming growth factor-beta1 (TGFβ1)- and epidermal growth factor (EGF)-induced EMT in PANC-1, AsPC-1, and BxPC-3 PC cell lines, along with the inhibition of TGFβ1- and EGF-induced EMT-like cell morphology and invasion, down-regulation of E-cad, and up-regulation of MMP9 and Vimentin in those 3 cell lines, respectively.
Gli1 silencing alone has no effect on EMT initiation; however, it exerts a protumor role in the aggressive invasion of PC cells by promoting TGFβ1- and EGF-induced EMT.
刺猬信号通路及其关键靶效应因子Gli1与多种癌症中上皮-间质转化（EMT）的发生密切相关。然而，Gli1在调节胰腺癌（PC）EMT中的具体作用仍不清楚。
在细胞和组织水平上，我们研究了Gli1在有无外部刺激处理情况下对PC中EMT起始的作用。
免疫组织化学结果显示，Gli1与基质金属蛋白酶9（MMP9）呈正相关，而与E-钙黏蛋白（E-cad）或波形蛋白无关。Gli1表达与肿瘤T分期（P = 0.025）和国际癌症控制联盟分期（P = 0.032）呈正相关，而MMP9表达与淋巴结转移（P = 0.017）和国际癌症控制联盟分期（P = 0.006）呈正相关。此外，Gli1和MMP9共表达的患者总生存期较差（P = 0.015）。在没有外部刺激的情况下，单独沉默Gli1对EMT没有影响，但可抑制转化生长因子-β1（TGFβ1）和表皮生长因子（EGF）诱导的PANC-1、AsPC-1和BxPC-3 PC细胞系中的EMT，同时抑制TGFβ1和EGF诱导的EMT样细胞形态和侵袭，下调这3种细胞系中的E-cad，并上调MMP9和波形蛋白。
单独沉默Gli1对EMT起始没有影响；然而，它通过促进TGFβ1和EGF诱导的EMT在PC细胞的侵袭性生长中发挥促肿瘤作用。
