Cellular prion protein promotes glucose uptake through the Fyn-HIF-2α-Glut1 pathway to support colorectal cancer cell survival
| Autor: | Jun-Hui Ge, Xin-Yun Xu, Yan-Ping Sun, Qing-Quan Li, Qiang Wang, Can-Ping Ruan, Zu-De Xu, Wenchao Gao, Jin He |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
medicine.medical_specialty Chromatin Immunoprecipitation Tumor suppressor gene Cell Survival animal diseases Glucose uptake Immunoblotting Mice Nude Adenocarcinoma Proto-Oncogene Proteins c-fyn Polymerase Chain Reaction Mice FYN Downregulation and upregulation Internal medicine mental disorders medicine Basic Helix-Loop-Helix Transcription Factors Gene silencing Animals Humans PrPC Proteins Gene knockdown Glucose Transporter Type 1 biology Glucose transporter General Medicine Xenograft Model Antitumor Assays nervous system diseases Cell biology Endocrinology Glucose Oncology Microscopy Fluorescence biology.protein GLUT1 Female Colorectal Neoplasms Signal Transduction |
| Zdroj: | Cancer science. 102(2) |
| ISSN: | 1349-7006 |
| Popis: | Cellular prion protein (PrPc) is a glycosylphosphatidylinositol-anchored membrane protein that has various physical functions, including protection against apoptotic and oxidative stress, cellular uptake of copper ions, transmembrane signaling, and adhesion to the extracellular matrix. In this study, we show that PrPc is highly expressed in colorectal adenocarcinomas. Transcriptome profiling of PrPc-depleted DLD-1 cells revealed downregulation of glucose transporter 1 (Glut1). PrPc is shown to be involved in regulating Glut1 expression through the Fyn-HIF-2α pathway. As Glut1 is the natural transporter of glucose and is required for the high glycolytic rate seen in colorectal tumors, silencing of PrPc reduced the proliferation and survival rate of colorectal cancer cells in vitro. In vivo, knockdown of PrPc by hydrodynamic injection with a cocktail of PrPc–shRNA-encoding plasmids also inhibited tumorigenicity in a xenograft model in nude mice. In summary, our data characterize a novel molecular mechanism that links PrPc expression to the regulation of glycolysis. Targeting PrPc will therefore be a promising strategy to overcome the growth and survival advantage in colorectal tumors. (Cancer Sci 2011; 102: 400–406) |
| Databáze: | OpenAIRE |
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