Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
J Transl Med. 2011 Jun 25;9:97. doi: 10.1186/1479-5876-9-97.
Protein kinase CK2 is a highly conserved, ubiquitous protein serine/threonine kinase that phosphorylates many substrates and has a global role in numerous biological and pathological processes. Overexpression of the protein kinase CK2α subunit (CK2α) has been associated with the malignant transformation of several tissues, with not nearly as much focus on the role of CK2α in colorectal cancer (CRC). The aims of this study are to investigate the function and regulatory mechanism of CK2α in CRC development.
Expression levels of CK2α were analyzed in 144 patients (104 with CRC and 40 with colorectal adenoma) by immunohistochemistry. Proliferation, senescence, motility and invasion assays as well as immunofluorescence staining and western blots were performed to assess the effect of CK2α in CRC.
The immunohistochemical expression of nuclear CK2α was stronger in tumor tissues than in adenomas and normal colorectal tissues. Suppression of CK2α by small-interfering RNA or the CK2α activity inhibitor emodin inhibited proliferation of CRC cells, caused G0/G1 phase arrest, induced cell senescence, elevated the expression of p53/p21 and decreased the expression of C-myc. We also found that knockdown of CK2α suppressed cell motility and invasion. Significantly, CK2α inhibition resulted in β-catenin transactivation, decreased the expression levels of vimentin and the transcription factors snail1 and smad2/3, and increased the expression of E-cadherin, suggesting that CK2α regulates the epithelial-mesenchymal transition (EMT) process in cancer cells.
Our results indicate that CK2α plays an essential role in the development of CRC, and inhibition of CK2α may serve as a promising therapeutic strategy for human CRC.
蛋白激酶 CK2 是一种高度保守、普遍存在的蛋白丝氨酸/苏氨酸激酶，可磷酸化许多底物，并在许多生物和病理过程中发挥全局作用。蛋白激酶 CK2α 亚基（CK2α）的过表达与几种组织的恶性转化有关，但对 CK2α 在结直肠癌（CRC）中的作用关注甚少。本研究旨在探讨 CK2α 在 CRC 发展中的功能和调节机制。
采用免疫组织化学法分析 144 例患者（104 例 CRC 患者和 40 例结直肠腺瘤患者）中 CK2α 的表达水平。通过增殖、衰老、运动和侵袭测定以及免疫荧光染色和 Western blot 分析评估 CK2α 对 CRC 的影响。
核 CK2α 的免疫组织化学表达在肿瘤组织中强于腺瘤和正常结直肠组织。通过小干扰 RNA 或 CK2α 活性抑制剂大黄素抑制 CK2α 的表达抑制 CRC 细胞的增殖，导致 G0/G1 期阻滞，诱导细胞衰老，上调 p53/p21 的表达，降低 C-myc 的表达。我们还发现，CK2α 的敲低抑制了细胞的运动和侵袭。重要的是，CK2α 抑制导致β-连环蛋白的反式激活，降低波形蛋白和转录因子 snail1 和 smad2/3 的表达水平，并增加 E-钙粘蛋白的表达，表明 CK2α 调节癌细胞的上皮-间质转化（EMT）过程。
我们的研究结果表明，CK2α 在 CRC 的发生发展中起着重要作用，抑制 CK2α 可能成为人类 CRC 的一种有前途的治疗策略。
