title: Advanced glycation end products increase carbohydrate responsive element binding protein expression and promote cancer cell proliferation.
abstract: Diabetic patients have increased levels of advanced glycation end products (AGEs) and the role of AGEs in regulating cancer cell proliferation is unclear. Here, we found that treating colorectal and liver cancer cells with AGEs promoted cell proliferation. AGEs stimulated both the expression and activation of a key transcription factor called carbohydrate responsive element binding protein (ChREBP) which had been shown to promote glycolytic and anabolic activity as well as proliferation of colorectal and liver cancer cells. Using siRNAs or the antagonistic antibody for the receptor for advanced glycation end-products (RAGE) blocked AGEs-induced ChREBP expression or cell proliferation in cancer cells. Suppressing ChREBP expression severely impaired AGEs-induced cancer cell proliferation. Taken together, these results demonstrate that AGEs-RAGE signaling enhances cancer cell proliferation in which AGEs-mediated ChREBP induction plays an important role. These findings may provide new explanation for increased cancer progression in diabetic patients.
authors.affiliation: Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665, Kong Jiang Road, Shanghai, 200092, China.
authors.forename: Hanbei
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025, China.
authors.forename: Yakui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Meng
authors.affiliation: Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665, Kong Jiang Road, Shanghai, 200092, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025, China; Department of Physiology, Dalian Medical University, 9 Xiduan, Lvshun South Road, Dalian, Liaoning Province, 116044, China.
authors.forename: Dianqiang
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025, China.
authors.forename: Yemin
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665, Kong Jiang Road, Shanghai, 200092, China.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025, China.
authors.forename: Minle
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, 280 S. Chongqing Road, Shanghai, 200025, China. Electronic address: xuemeitong@shsmu.edu.cn.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Tong
authors.affiliation: Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665, Kong Jiang Road, Shanghai, 200092, China. Electronic address: suqing139@126.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Su
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000096:biosynthesis*; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D017127:Glycation End Products, Advanced; C116385:MLXIPL protein, human; D009363:Neoplasm Proteins; D000067759:Receptor for Advanced Glycation End Products
keywords: Advanced glycation end products; Cancer; Carbohydrate responsive element binding protein; Diabetes mellitus; Proliferation; Receptor for advanced glycation end-products