Why cancer or tumor loves sugar?

Chunming Cheng, Peng Ru, Feng Geng, Junfeng Liu, Ji Young Yoo, Xiaoning Wu, Xiang Cheng, Vanessa Euthine, Peng Hu, Jeffrey Yunhua Guo, Etienne Lefai, Balveen Kaur, Axel Nohturfft, Jianjie Ma, Arnab Chakravarti, Deliang Guo

Overview

Elevated glucose consumption and active lipogenesis are a common patho-physiological characteristic of cancer. We elutriated for the first time the link between glucose supply and sterol SREBP pathway, which controlling lipid metabolism. In this study, we delineate that EGFR signaling, by increasing glucose uptake, promotes SCAP N-glycosylation, and consequent proteolytic activation of SREBP.

Summary

SCAP acts as a key glucose-responsive protein to integrate oncogenic signaling and fuel availability for the control of lipid metabolism and tumor growth. Targeting SCAP N-glycosylation may provide a promising means of treating malignancies and metabolic diseases with deregulated lipid metabolism, such as atherosclerosis, obesity, and diabetes.

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Author Comments

Dr. Chunming Cheng, PhD
Dr. Chunming Cheng, PhD
The Ohio State University
Senior Research Associate
biochemistry
Columbus, OH | United States
I spend the most energy on this study (this finding has been recognized by the American Cancer Society as one of “Ten Key Breakthroughs and Insights” in 2015). I hope this article can inspire or help more people to understand cancer. Starting from this finding, the deepening dig will help to kill cancer in the future.Dr. Chunming Cheng, PhD

Resources

original research article
http://dx.doi.org/10.1016/j.ccell.2015.09.021
Previewed in Cancer Cell
https://www.cell.com/cancer-cell/fulltext/S1535-6108(15)00388-8
SCAP links glucose to lipids for tumor growth
https://cancerres.aacrjournals.org/content/76/14_Supplement/25

Glucose-Mediated N-glycosylation of SCAP Is Essential for SREBP-1 Activation and Tumor Growth.

Authors:
Dr. Chunming Cheng, PhD
Dr. Chunming Cheng, PhD
The Ohio State University
Senior Research Associate
biochemistry
Columbus, OH | United States
Dr. Xiang Cheng, PhD
Dr. Xiang Cheng, PhD
Ohio State University

, | United States
Etienne Lefai, PhD
Etienne Lefai, PhD
INRA
Research scientist
Muscle homeostasis
Clermont Ferrand | France

Cancer Cell 2015 Nov;28(5):569-581

Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA. Electronic address:

Tumorigenesis is associated with increased glucose consumption and lipogenesis, but how these pathways are interlinked is unclear. Here, we delineate a pathway in which EGFR signaling, by increasing glucose uptake, promotes N-glycosylation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and consequent activation of SREBP-1, an ER-bound transcription factor with central roles in lipid metabolism. Glycosylation stabilizes SCAP and reduces its association with Insig-1, allowing movement of SCAP/SREBP to the Golgi and consequent proteolytic activation of SREBP. Xenograft studies reveal that blocking SCAP N-glycosylation ameliorates EGFRvIII-driven glioblastoma growth. Thus, SCAP acts as key glucose-responsive protein linking oncogenic signaling and fuel availability to SREBP-dependent lipogenesis. Targeting SCAP N-glycosylation may provide a promising means of treating malignancies and metabolic diseases.

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Source
http://dx.doi.org/10.1016/j.ccell.2015.09.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643405PMC
November 2015
213 Reads
30 Citations
23.523 Impact Factor

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