title: Systematic network assessment of the carcinogenic activities of cadmium.
abstract: Cadmium has been defined as type I carcinogen for humans, but the underlying mechanisms of its carcinogenic activity and its influence on protein-protein interactions in cells are not fully elucidated. The aim of the current study was to evaluate, systematically, the carcinogenic activity of cadmium with systems biology approaches. From a literature search of 209 studies that performed with cellular models, 208 proteins influenced by cadmium exposure were identified. All of these were assessed by Western blotting and were recognized as key nodes in network analyses. The protein-protein functional interaction networks were constructed with NetBox software and visualized with Cytoscape software. These cadmium-rewired genes were used to construct a scale-free, highly connected biological protein interaction network with 850 nodes and 8770 edges. Of the network, nine key modules were identified and 60 key signaling pathways, including the estrogen, RAS, PI3K-Akt, NF-κB, HIF-1α, Jak-STAT, and TGF-β signaling pathways, were significantly enriched. With breast cancer, colorectal and prostate cancer cellular models, we validated the key node genes in the network that had been previously reported or inferred form the network by Western blotting methods, including STAT3, JNK, p38, SMAD2/3, P65, AKT1, and HIF-1α. These results suggested the established network was robust and provided a systematic view of the carcinogenic activities of cadmium in human.
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Peizhan
authors.initials: P
authors.lastname: Chen
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Duan
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Mian
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Huang
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China.
authors.forename: Jingquan
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China.
authors.forename: Ruiai
authors.initials: R
authors.lastname: Chu
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Song
authors.affiliation: Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Jia
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China. Electronic address: qba@sibs.ac.cn.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ba
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing, China; School of Life Science and Technology, ShanghaiTech University, Shanghai, China. Electronic address: huiwang@sibs.ac.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D002104:Cadmium / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D049490:Systems Biology
chemical_list: D002273:Carcinogens; D002104:Cadmium
keywords: Cadmium; Carcinogenesis; Network assessment