Cyr61 promotes growth of pancreatic carcinoma via nuclear exclusion of p27
Cyr61 promotes growth of pancreatic carcinoma via nuclear exclusion of p27
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Cyr61 通过 p27 的核排斥促进胰腺癌的生长
DOI：
10.1007/s13277-014-2423-x
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发表时间：
2014-11-01
期刊：
影响因子：
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通讯作者：
Meng, Zhiqiang
中科院分区：
文献类型：
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作者：
Shi, Weidong;Yin, Jianhua;Meng, Zhiqiang
胰腺癌(PCC)生长的分子调控机制复杂，目前尚不清楚。在这里，我们显示富含半胱氨酸的蛋白61(Cyr61)在PCC中的水平显著高于来自同一患者的邻近非肿瘤组织。Cyr61过表达促进了PCC细胞的增殖，而抑制Cyr61则抑制了PCC细胞的增殖。进一步分析表明，Cyr61似乎激活了PCC细胞中的磷脂酰肌醇3-激酶(PI3K)，但不能激活细胞外相关激酶/丝裂原活化蛋白激酶(ERK/MAPK)信号通路，从而导致主要的细胞周期抑制物p27的核排斥，从而促进了细胞的增殖。综上所述，这些发现揭示了Cyr61调控PCC增殖的分子基础，提示了Cyr61在PCC生长中的潜在作用，并强调了Cyr61作为PCC治疗的新靶点。
The molecular regulation of the growth of pancreatic carcinoma (PCC) is complicated and not defined yet. Here we show that the cysteine-rich protein 61 (Cyr61) levels were significantly higher in PCC than in the adjacent nontumor tissues from the same human patient. Overexpression of Cyr61 enhanced the proliferation of PCC cells, while inhibition of Cyr61 decreased the proliferation of PCC cells. Further analysis showed that Cyr61 seemed to activate phosphatidylinositol 3-kinase (PI3K) but not extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway in PCC cells, which subsequently induced nuclear exclusion of a major cell cycle inhibitor, p27, to increase cell proliferation. Taken together, these findings reveal the molecular basis underlying Cyr61-regulated PCC proliferation, suggest a potential role of Cyr61 in PCC growth, and highlight Cyr61 as a novel target for PCC therapy.