Par3 regulates invasion of pancreatic cancer cells via interaction with Tiam1
Par3 regulates invasion of pancreatic cancer cells via interaction with Tiam1
复制标题
Par3 通过与 Tiam1 相互作用调节胰腺癌细胞的侵袭
DOI：
10.1007/s10238-015-0365-2
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发表时间：
2016-08-01
影响因子：
4.6
通讯作者：
Qin, Renyi
中科院分区：
文献类型：
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作者：
Guo, Xingjun;Wang, Min;Qin, Renyi
保守的极性复合体由分裂缺陷蛋白PAR3、PAR6和非典型蛋白激酶C组成，影响各种细胞极化事件，包括紧密连接的组装。紧密连接组装的控制与侵入和运移潜力密切相关。然而，由于保守的极性复合体在调节胰腺癌侵袭和转移中的重要性尚不清楚，我们研究了它们在胰腺癌中的作用和机制。我们首先检测了保守的极性复合体的关键蛋白，发现只有Par3在胰腺癌组织中下调，而Par6和aPKC没有差异。更重要的是，PAR3组织水平与患者总生存期显著正相关。下调PAR3基因可促进胰腺癌细胞的侵袭和迁移。而Par3需要与Tiam1相互作用，影响紧密连接组装，进而影响胰腺癌细胞的侵袭和迁移。随后，我们发现紧密连接标志蛋白ZO-1和Claudin-1在胰腺癌组织中表达下调。胰腺癌组织中Par3和ZO-1的表达呈直线相关。我们建立了人胰腺癌细胞在Balb/c裸鼠体内的肝转移模型，发现敲除Par3促进了体内的侵袭和转移，并干扰了紧密连接的组装。综上所述，这些结果表明，Par3通过控制紧密连接组装来调控胰腺癌的侵袭和转移。
The conserved polarity complex, which comprises partitioning-defective proteins Par3, Par6, and the atypical protein kinase C, affects various cell-polarization events, including assembly of tight junctions. Control of tight junction assembly is closely related to invasion and migration potential. However, as the importance of conserved polarity complexes in regulating pancreatic cancer invasion and metastasis is unclear, we investigated their role and mechanism in pancreatic cancers. We first detect that the key protein of the conserved polarity complex finds that only Par3 is down-regulated in pancreatic cancer tissues while Par6 and aPKC show no difference. What is more, Par3 tissues level was significantly and positively associated with patient overall survival. Knocking-down Par3 promotes pancreatic cancer cells invasion and migration. And Par3 requires interaction with Tiam1 to affect tight junction assembly, and then affect invasion and migration of pancreatic cancer cells. Then, we find that tight junction marker protein ZO-1 and claudin-1 are down-regulated in pancreatic cancer tissues. And the relationship of the expression of Par3 and ZO-1 in pancreatic cancer tissue is linear correlation. We establish liver metastasis model of human pancreatic cancer cells in Balb/c nude mice and find that knocking down Par3 promotes invasion and metastasis and disturbs tight junction assembly in vivo. Taken together, these results suggest that the Par3 regulates invasion and metastasis in pancreatic cancers by controlling tight junction assembly.