Nathalie Vaes1, Simone L Schonkeren2, Erwin Brosens3, Alexander Koch4, Conor J McCann5, Nikhil Thapar6, Robert M W Hofstra7, Manon van Engeland8, Veerle Melotte9. 1. Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, The Netherlands. Electronic address: n.vaes@maastrichtuniversity.nl. 2. Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, The Netherlands. Electronic address: s.schonkeren@student.maastrichtuniversity.nl. 3. Department of Clinical Genetics, University of Rotterdam, EMC, Rotterdam, The Netherlands. Electronic address: e.brosens@erasmusmc.nl. 4. Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, The Netherlands. Electronic address: a.koch@maastrichtuniversity.nl. 5. Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health, London WC1N, UK. Electronic address: conor.mccann@ucl.ac.uk. 6. Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health, London WC1N, UK. Electronic address: n.thapar@ucl.ac.uk. 7. Department of Clinical Genetics, University of Rotterdam, EMC, Rotterdam, The Netherlands. Electronic address: r.hofstra@erasmusmc.nl. 8. Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, The Netherlands. Electronic address: m.vanengeland@maastrichtuniversity.nl. 9. Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, The Netherlands; Department of Clinical Genetics, University of Rotterdam, EMC, Rotterdam, The Netherlands. Electronic address: veerle.melotte@maastrichtuniversity.nl.
Abstract
BACKGROUND: The N-Myc Downstream-Regulated Gene (NDRG) family comprises four members that function in cellular processes like proliferation and differentiation. While NDRG1 and NDRG2 are extensively studied, knowledge regarding NDRG3 and NDRG4, despite its recognition as a well-established early-detection marker for colorectal cancer (Cologuard®), is sparse. SCOPE OF REVIEW: To summarize expression, biomarker potential and functional mechanisms of the NDRGs in the developing, mature and cancerous gut, we combine current literature and in silico analyses from the TCGA-database, GTEX Project, E14.5 mouse intestine and enteric neural crest cells, and an RNA-sequencing time-series of human embryonic colonic samples. MAJOR CONCLUSIONS: This study reveals that all members display a differential expression pattern in the gut and that NDRG1, NDRG2 and NDRG4 (1) can serve as biomarker for colorectal cancer and (2) have tumor suppressive properties mainly affecting cell proliferation and epithelial-mesenchymal transition. GENERAL SIGNIFICANCE: Similar effects of the NDRGs on the key-hallmarks of cancer, could implicate analogous functions in other tissue/cancer types.
BACKGROUND: The N-Myc Downstream-Regulated Gene (NDRG) family comprises four members that function in cellular processes like proliferation and differentiation. While NDRG1 and NDRG2 are extensively studied, knowledge regarding NDRG3 and NDRG4, despite its recognition as a well-established early-detection marker for colorectal cancer (Cologuard®), is sparse. SCOPE OF REVIEW: To summarize expression, biomarker potential and functional mechanisms of the NDRGs in the developing, mature and cancerous gut, we combine current literature and in silico analyses from the TCGA-database, GTEX Project, E14.5 mouse intestine and enteric neural crest cells, and an RNA-sequencing time-series of humanembryonic colonic samples. MAJOR CONCLUSIONS: This study reveals that all members display a differential expression pattern in the gut and that NDRG1, NDRG2 and NDRG4 (1) can serve as biomarker for colorectal cancer and (2) have tumor suppressive properties mainly affecting cell proliferation and epithelial-mesenchymal transition. GENERAL SIGNIFICANCE: Similar effects of the NDRGs on the key-hallmarks of cancer, could implicate analogous functions in other tissue/cancer types.
Authors: Nathalie Vaes; Simone L Schonkeren; Glenn Rademakers; Amy M Holland; Alexander Koch; Marion J Gijbels; Tom G Keulers; Meike de Wit; Laura Moonen; Jaleesa R M Van der Meer; Edith van den Boezem; Tim G A M Wolfs; David W Threadgill; Jeroen Demmers; Remond J A Fijneman; Connie R Jimenez; Pieter Vanden Berghe; Kim M Smits; Kasper M A Rouschop; Werend Boesmans; Robert M W Hofstra; Veerle Melotte Journal: EMBO Rep Date: 2021-04-23 Impact factor: 8.807