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Reduced signaling of PI3K-Akt and RAS-MAPK pathways is the key target for weight-loss-induced cancer prevention by dietary calorie restriction and/or physical activity

文献类型： 外文期刊

作者： Standard, Joseph 1 ; Jiang, Yu 1 ; Yu, Miao 1 ; Su, Xiaoyu 1 ; Zhao, Zhihui 2 ; Xu, Jianteng 1 ; Chen, Jie 1 ; King, Bren 1 ;

作者机构： 1.Kansas State Univ, Dept Human Nutr, Manhattan, KS 66506 USA

2.Shanghai Acad Agr Sci, Inst Agri food Stand & Testing Technol, Shanghai 201403, Peoples R China

3.Zhejiang Acad Agr Sci, Inst Anim Husb & Vet Sci, Hangzhou 310021, Zhejiang, Peoples R China

4.Kansas State Univ, Dept Biochem, Manhattan, KS 66506 USA

5.Wheaton Coll, Dept Appl Hlth Sci, Wheaton, IL 60187 USA

关键词： Bioinformatics;Weigh control;Cancer prevention;Dietary calorie restriction;Exercise

期刊名称：JOURNAL OF NUTRITIONAL BIOCHEMISTRY （ 影响因子：6.048； 五年影响因子：6.114 ）

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收录情况： SCI

摘要： Weight control through either dietary calorie restriction (DCR) or exercise has been associated with cancer prevention in animal models. However, the underlying mechanisms are not fully defined. Bioinformatics using genomics, proteomics and lipidomics was employed to elucidate the molecular targets of weight control in a mouse skin cancer model. SENCAR mice were randomly assigned into four groups for 10 weeks: ad-libitum-fed sedentary control, ad-libitum-fed exercise (AE), exercise but pair-fed isocaloric amount of control (PE) and 20% DCR. Two hours after topical TPA treatment, skin epidermis was analyzed by Affymetrix for gene expression, DIGE for proteomics and lipidomics for phospholipids. Body weights were significantly reduced in both DCR and PE but not AE mice versus the control. Among 39,000 transcripts, 411, 67 and 110 genes were significantly changed in DCR, PE and AE, respectively. The expression of genes relevant to PI3K-Akt and Ras-MAPK signaling was effectively reduced by DCR and PE but not AE as measured through GenMAPP software. Proteomics analysis identified similar to 120 proteins, with 27 proteins significantly changed by DCR, including up-regulated apolipoprotein A-1, a key antioxidant protein that decreases Ras-MAPK activity. Of the total 338 phospholipids analyzed by lipidomics, 57 decreased by PE including 5 phophatidylinositol species that serve as PI3K substrates. Although a full impact has not been determined yet, it appears that the reduction of both Ras-MAPK and PI3K-Akt signaling pathways is a cancer preventive target that has been consistently demonstrated by three bioinformatics approaches. (C) 2014 Elsevier Inc. All rights reserved.

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