Protein Kinase Casein Kinase 2-Mediated Upregulation of N-Cadherin Confers Anoikis Resistance on Esophageal Carcinoma Cells
Protein Kinase Casein Kinase 2-Mediated Upregulation of N-Cadherin Confers Anoikis Resistance on Esophageal Carcinoma Cells
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DOI：
10.1158/1541-7786.mcr-12-0261
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发表时间：
2012-08-01
影响因子：
5.2
通讯作者：
Kim, Kunhong
中科院分区：
文献类型：
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作者：
Ko, Hyeonseok;Kim, Seongrak;Kim, Kunhong
此前，我们报道了高 PKCK2 活性可以通过 procaspase-2 的磷酸化来保护癌细胞免受死亡受体介导的细胞凋亡。由于失巢凋亡是细胞凋亡的另一种形式，我们想知道 PKCK2 是否可以类似地赋予癌细胞对失巢凋亡的抵抗力。具有高 PKCK2 活性的人食管鳞癌细胞系（HCE4 和 HCE7）具有抗失巢凋亡的能力，而具有低 PKCK2 活性的细胞系（TE2 和 TE3）对失巢凋亡敏感。由于细胞对失巢凋亡表现出不同的敏感性，我们使用cDNA微阵列比较了失巢凋亡敏感的TE2和抗失巢凋亡的HCE4细胞之间细胞粘附分子的表达。我们发现E-cadherin仅在TE2细胞中表达；而 HCE4 细胞中表达的是 N-钙粘蛋白，而不是 E-钙粘蛋白。为了检查 PKCK2 活性是否可以决定钙粘蛋白表达的类型，我们首先通过使用慢病毒过表达 PKCK2 α 催化亚基来增加 TE2 细胞中的细胞内 PKCK2 活性，并发现高 PKCK2 活性可以将钙粘蛋白表达从 E 型转变为 N 型并赋予失巢凋亡抗性。相反，通过使用 shRNA 敲低 PKCK2 α 催化亚基，HCE4 细胞中 PKCK2 活性降低，诱导 N-钙粘蛋白向 E-钙粘蛋白转换，失巢凋亡抗性细胞变得敏感。此外，N-钙粘蛋白表达与 PKB/Akt 激活和侵袭性增加相关。我们得出的结论是，高细胞内 PKCK2 活性通过诱导 E-钙粘蛋白转换为 N-钙粘蛋白，赋予食管癌细胞失巢凋亡抵抗力。摩尔癌症研究中心； 10（8）； 1032-8。 (c) 2012 年 AACR。
Previously, we reported that high PKCK2 activity could protect cancer cells from death receptor-mediated apoptosis through phosphorylation of procaspase-2. Because anoikis is another form of apoptosis, we asked whether PKCK2 could similarly confer resistance to anoikis on cancer cells. Human esophageal squamous cancer cell lines with high PKCK2 activity (HCE4 and HCE7) were anoikis-resistant, whereas cell lines with low PKCK2 activity (TE2 and TE3) were anoikis-sensitive. Because the cells showed different sensitivity to anoikis, we compared the expression of cell adhesion molecules between anoikis-sensitive TE2 and anoikis-resistant HCE4 cells using cDNA microarray. We found that E-cadherin is expressed only in TE2 cells; whereas N-cadherin is expressed instead of E-cadherin in HCE4 cells. To examine whether PKCK2 activity could determine the type of cadherin expressed, we first increased intracellular PKCK2 activity in TE2 cells by overexpressing the PKCK2 alpha catalytic subunit using lentivirus and found that high PKCK2 activity could switch cadherin expression from type E to N and confer anoikis resistance. Conversely, a decrease in PKCK2 activity in HCE4 cells by knockdown of PKCK2 alpha catalytic subunit using shRNA induced N- to E-cadherin switching and the anoikis-resistant cells became sensitive. In addition, N-cadherin expression correlated with PKB/Akt activation and increased invasiveness. We conclude that high intracellular PKCK2 activity confers anoikis resistance on esophageal cancer cells by inducing E- to N-cadherin switching. Mol Cancer Res; 10(8); 1032-8. (c) 2012 AACR.