Pyruvate kinase M2 facilitates colon cancer cell migration via the modulation of STAT3 signalling
Pyruvate kinase M2 facilitates colon cancer cell migration via the modulation of STAT3 signalling
复制标题
丙酮酸激酶 M2 通过调节 STAT3 信号传导促进结肠癌细胞迁移
DOI：
10.1016/j.cellsig.2014.03.020
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发表时间：
2014-09-01
影响因子：
4.8
通讯作者：
Li, Zhuoyu
中科院分区：
文献类型：
--
作者：
Yang, Peng;Li, Zongwei;Li, Zhuoyu
了解结直肠癌（CRC）转移进展的机制对于降低其发病率和死亡率至关重要。丙酮酸激酶（PK）催化糖酵解的最后一步，并已被确定为葡萄糖消耗的关键调节剂。然而，PKM 1和PKM 2在调节CRC细胞迁移和细胞粘附中的机制和作用仍不清楚。在这里，我们报告PKM 2而不是PKM 1驱动CRC细胞迁移和细胞粘附，而PKM衰减逆转这些现象。此外，PKM 2的过表达显著增加了N-钙粘蛋白、MMP-2、MMP-9、STAT 3、Snail-2、pFAK和活性β 1-整合素的表达，而E-钙粘蛋白的表达被抑制。更重要的是，结果表明PKM 2过表达促进STAT 3核转位，并且PKM 2在调节迁移和粘附相关信号传导中的功能是必需的。此外，PKM 2的二聚体形式，其缺乏丙酮酸激酶活性，但具有蛋白激酶活性，对于CRC细胞迁移和细胞粘附至关重要。总体而言;该研究表明PKM 2过表达通过调节STAT 3相关信号传导促进CRC细胞迁移和细胞粘附，PKM 2可作为CRC转移的治疗靶点。(C)2014爱思唯尔公司All rights reserved.
Understanding the mechanisms of colorectal cancer (CRC) metastatic progression is essential to reducing its morbidity and mortality. Pyruvate kinase (PK) catalyses the final step of glycolysis and has been identified as a critical regulator of glucose consumption. However, the mechanisms and roles of PKM1 and PKM2 in the regulation of CRC cell migration and cell adhesion remain elusive. Here, we report that PKM2 rather than PKM1 drives CRC cell migration and cell adhesion, whereas PKM attenuation reverses these phenomena. Furthermore, the overexpression of PKM2 significantly increases the expression of N-cadherin, MMP-2, MMP-9, STAT3, Snail-2, pFAK and active beta 1-integrin, while E-cadherin expression is suppressed. More importantly, the results indicated that PKM2 overexpression facilitates STAT3 nuclear translocation, and it is required for PKM2 function in the regulation of migration and adhesion associated signalling. In addition, the dimeric form of PKM2, which lacks the pyruvate kinase activities but possesses protein kinase activity, is critical for CRC cell migration and cell adhesion. Overall; this study suggests that PKM2 overexpression promotes CRC cell migration and cell adhesion by regulating STAT3-associated signalling and that PKM2 may serve as a therapeutic target for CRC metastasis. (C) 2014 Elsevier Inc. All rights reserved.