钙调蛋白依赖性蛋白激酶激酶2——胃腺癌的新型治疗靶点
Calcium calmodulin dependent kinase kinase 2 - a novel therapeutic target for gastric adenocarcinoma.
作者信息
Subbannayya Yashwanth, Syed Nazia, Barbhuiya Mustafa A, Raja Remya, Marimuthu Arivusudar, Sahasrabuddhe Nandini, Pinto Sneha M, Manda Srikanth Srinivas, Renuse Santosh, Manju H C, Zameer Mohammed Abdul Lateef, Sharma Jyoti, Brait Mariana, Srikumar Kotteazeth, Roa Juan Carlos, Vijaya Kumar M, Kumar K V Veerendra, Prasad T S Keshava, Ramaswamy Girija, Kumar Rekha Vijay, Pandey Akhilesh, Gowda Harsha, Chatterjee Aditi
机构信息
a Institute of Bioinformatics ; International Technology Park ; Bangalore , India.
出版信息
Cancer Biol Ther. 2015;16(2):336-45. doi: 10.4161/15384047.2014.972264.
Gastric cancer is one of the most common gastrointestinal malignancies and is associated with poor prognosis. Exploring alterations in the proteomic landscape of gastric cancer is likely to provide potential biomarkers for early detection and molecules for targeted therapeutic intervention. Using iTRAQ-based quantitative proteomic analysis, we identified 22 proteins that were overexpressed and 17 proteins that were downregulated in gastric tumor tissues as compared to the adjacent normal tissue. Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was found to be 7-fold overexpressed in gastric tumor tissues. Immunohistochemical labeling of tumor tissue microarrays for validation of CAMKK2 overexpression revealed that it was indeed overexpressed in 94% (92 of 98) of gastric cancer cases. Silencing of CAMKK2 using siRNA significantly reduced cell proliferation, colony formation and invasion of gastric cancer cells. Our results demonstrate that CAMKK2 signals in gastric cancer through AMPK activation and suggest that CAMKK2 could be a novel therapeutic target in gastric cancer.
胃癌是最常见的胃肠道恶性肿瘤之一，且预后较差。探索胃癌蛋白质组图谱的变化可能会为早期检测提供潜在的生物标志物，并为靶向治疗干预提供分子靶点。通过基于iTRAQ的定量蛋白质组分析，我们鉴定出与相邻正常组织相比，胃癌组织中有22种蛋白质表达上调，17种蛋白质表达下调。发现钙/钙调蛋白依赖性蛋白激酶激酶2（CAMKK2）在胃癌组织中过表达7倍。对肿瘤组织微阵列进行免疫组织化学标记以验证CAMKK2的过表达，结果显示在94%（98例中的92例）的胃癌病例中它确实过表达。使用siRNA沉默CAMKK2可显著降低胃癌细胞的增殖、集落形成和侵袭。我们的结果表明，CAMKK2在胃癌中通过激活AMPK发出信号，并提示CAMKK2可能是胃癌的一个新的治疗靶点。
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