Stiehopus japonieus acidic mucopolysaccharide inhibits the proliferation of pancreatic cancer SW1990 cells through Hippo-YAP pathway.
Stiehopus japonieus acidic mucopolysaccharide inhibits the proliferation of pancreatic cancer SW1990 cells through Hippo-YAP pathway.
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DOI：
10.18632/oncotarget.14633
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发表时间：
2017-03-07
期刊：
影响因子：
--
通讯作者：
Tian Z
中科院分区：
文献类型：
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作者：
Li X;Liu Y;Zhang C;Niu Q;Wang H;Che C;Xie M;Zhou B;Xu Y;Zhang Q;Wu J;Tian Z
以往研究表明，刺参酸性粘多糖（SJAMP）能抑制胰腺癌细胞SW 1990的增殖。然而，其机制仍不清楚。在我们的研究中，雅普的表达鉴定免疫组化和定量实时PCR从45对人类胰腺导管腺癌（PDAC）组织和其相邻的非肿瘤样本。发现雅普的表达与胰腺癌的组织分化程度有关，与胰腺癌患者的生存期呈负相关。胰腺癌组织中雅普定位于细胞核，雅普mRNA表达明显高于正常胰腺组织。这些结果表明雅普在胰腺癌的发病机制中起着惊人的调节作用。SJAMP作用后，随着作用时间的延长，雅普和TEAD 1表达下调，MST 1和p雅普表达逐渐上调。SJAMP还改善了雅普磷酸化、核质易位和失活。成功敲低雅普siRNA后，SJAMP对癌细胞增殖的抑制作用减弱。有趣的是，我们表明即使在雅普沉默后，用4mg/ml、8mg/ml SJAMP持续24小时和用8mg/ml SJAMP持续24小时、48小时的TEAD下调。这可能意味着SJAMP有其他靶点，而不仅仅是雅普，来下调TEAD。我们提出Hippo-YAP通路可能参与胰腺癌的发生和SJAMP对胰腺癌细胞增殖的抑制作用，但可能不是唯一的信号通路。
Previous studies have indicated that stiehopus japonieus acidic mucopolysaccharide (SJAMP) could inhibit the proliferation of pancreatic cancer cell SW1990. However, the mechanism remains unclear. In our study, YAP expression was identified by immunohistochemistry and quantitative Real-time PCR from 45 pairs of human pancreatic ductal adenocarcinoma (PDAC) tissues and their adjacent non-tumor samples. We found that the YAP expression was associated with the histological differentiation degree, and negatively correlated with pancreatic cancer patients’ survival. More YAP localization in nuclear and enhanced expression of YAP mRNA in pancreatic cancer tissue was found in comparison with in the normal tissue. These results identify YAP acts as an amazing regulator in the pathogenesis of pancreatic cancer. After affected by SJAMP, YAP and TEAD1 were down regulated, while MST1 and pYAP were upregulated gradually with the prolong of effect time. SJAMP also improved YAP phosphorylation, nuclear-to-cytoplasmic translocation and inactivation. After successfully knocked-down by YAP siRNA, the inhibition of proliferation of SJAMP to cancer cells was attenuated. Interestingly, we indicated a down-regulation of that TEAD with SJAMP 4 mg/ml, 8 mg/ml for 24 h and with 8 mg/ml SJAMP for 24 h, 48 h even after YAP silencing. That might mean that the SJAMP has other targets, not only YAP, to downregulate TEAD. We proposed a hypothesis that Hippo-YAP pathway involved in carcinogenesis of pancreatic cancer and in the inhibition effect of SJAMP to the proliferation of pancreatic cancer cell, although maybe not the sole signaling pathway.