Pyruvate kinase M2 plays a dual role on regulation of the EGF/EGFR signaling via E-cadherin-dependent manner in gastric cancer cells.
Pyruvate kinase M2 plays a dual role on regulation of the EGF/EGFR signaling via E-cadherin-dependent manner in gastric cancer cells.
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丙酮酸激酶 M2 在胃癌细胞中通过 E-钙粘蛋白依赖性方式调节 EGF/EGFR 信号传导发挥双重作用
DOI：
10.1371/journal.pone.0067542
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Guleng B
中科院分区：
文献类型：
--
作者：
Wang LY;Liu YP;Chen LG;Chen YL;Tan L;Liu JJ;Jazag A;Ren JL;Guleng B
背景和目的EGFR的激活和PKM2的表达在肿瘤发生中起重要作用。EGFR激活以亚细胞区室依赖的方式调节PKM2功能，促进基因转录和肿瘤生长。此外，在恶性胶质瘤中，PKM2在egfr诱导的通路中表达上调。然而，我们发现PKM2还可以调节胃癌细胞中EGF/EGFR信号通路的活性。我们的目的是明确PKM2调控细胞运动和侵袭的生物学机制。方法采用短发夹RNA稳定转染，稳定沉默BGC823、SGC7901和AGS胃癌细胞系中PKM2的表达。通过评估细胞迁移和侵袭来确定PKM2在体外的作用。免疫组化分析PKM2与其他蛋白的关系。结果在E-cadherin表达阳性的胃癌细胞系BGC823和SGC7901中，PKM2的表达降低了E-cadherin的活性，增强了EGF/EGFR信号通路。然而，在缺乏E-cadherin表达的未分化胃癌细胞系AGS中，PKM2促进细胞迁移和侵袭。免疫组化分析显示，E-cadherin表达水平、ERK1/2磷酸化水平和细胞质PKM2表达水平相互关联。结论：PKM2在不同分化的胃癌细胞类型中可能发挥着不同的作用，这一发现与以往的临床研究相一致。我们的研究结果揭示了在egfr刺激的胃癌细胞运动和侵袭过程中PKM2和E-cadherin之间的重要联系。
Background and Aims EGFR activation and PKM2 expression are instrumental in tumorigenesis. EGFR activation regulates PKM2 functions in a subcellular compartment-dependent manner and promotes gene transcription and tumor growth. In addition, PKM2 is upregulated in EGFR-induced pathways in glioma malignancies. However, we found that PKM2 could also regulate the activity of the EGF/EGFR signaling pathway in gastric cancer cells. We aimed to define the biological mechanisms for PKM2 in regulating the cell motility and invasion. Methods We employed stable transfection with short hairpin RNA to stably silence the expression of PKM2 in the BGC823, SGC7901 and AGS gastric cancer cell lines. The effects of PKM2 in vitro were determined by assessing cell migration and invasion. Immunohistochemical analysis was used to explore the relationship among PKM2 and other proteins. Results Our results indicate that the knockdown of PKM2 decreased the activity of E-cadherin and enhanced the EGF/EGFR signaling pathway in the gastric cell lines BGC823 and SGC7901 that were positive for E-cadherin expression. However, in the undifferentiated gastric carcinoma cell line AGS, which lacks E-cadherin expression, PKM2 promoted cell migration and invasion. Immunohistochemical analyses showed that the levels of E-cadherin expression, ERK1/2 phosphorylation, and cytoplasmic PKM2 expression were correlated with each other. Conclusion: PKM2 may play different roles in differently differentiated gastric cancer cell types, and this finding would be consistent with the previous clinical research. The results of our study reveal an important link between PKM2 and E-cadherin during EGFR-stimulated gastric cancer cell motility and invasion.
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影响因子：
6.3
作者：
Kitoh, T;Yanai, H;Okita, K
通讯作者：
Okita, K
影响因子：
4.8
作者：
Arora, PD;McCulloch, CAG
通讯作者：
McCulloch, CAG
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Piccolo, E;Innominato, PF;Falasca, M
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Falasca, M
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4.8
作者：
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OKADA, Y
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64.8
作者：
Guilford, P;Hopkins, J;Reeve, AE
通讯作者：
Reeve, AE