Advanced glycation end products increase carbohydrate responsive element binding protein expression and promote cancer cell proliferation

Hanbei Chen; Lifang Wu; Yakui Li; Jian Meng; Ning Lin; Dianqiang Yang; Yemin Zhu; Xiaoyong Li; Minle Li; Ye Xu; Yuchen Wu; Xuemei Tong; Qing Su

doi:10.1016/j.mce.2014.07.021

Advanced glycation end products increase carbohydrate responsive element binding protein expression and promote cancer cell proliferation

Mol Cell Endocrinol. 2014 Sep;395(1-2):69-78. doi: 10.1016/j.mce.2014.07.021. Epub 2014 Aug 8.

Authors

Hanbei Chen¹, Lifang Wu², Yakui Li², Jian Meng², Ning Lin¹, Dianqiang Yang³, Yemin Zhu², Xiaoyong Li¹, Minle Li², Ye Xu⁴, Yuchen Wu⁴, Xuemei Tong⁵, Qing Su⁶

Affiliations

¹ Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665, Kong Jiang Road, Shanghai, 200092, China.
² 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.
³ 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.
⁴ Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032, China.
⁵ 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: [email protected].
⁶ Department of Endocrinology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665, Kong Jiang Road, Shanghai, 200092, China. Electronic address: [email protected].

PMID: 25111846
DOI: 10.1016/j.mce.2014.07.021

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.

Keywords: Advanced glycation end products; Cancer; Carbohydrate responsive element binding protein; Diabetes mellitus; Proliferation; Receptor for advanced glycation end-products.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / biosynthesis*
Cell Proliferation*
Gene Expression Regulation, Neoplastic*
Glycation End Products, Advanced / metabolism*
Hep G2 Cells
Humans
Neoplasm Proteins / metabolism*
Neoplasms / metabolism*
Neoplasms / pathology
Receptor for Advanced Glycation End Products / metabolism

Substances

Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Glycation End Products, Advanced
MLXIPL protein, human
Neoplasm Proteins
Receptor for Advanced Glycation End Products