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CYB5R1 links epithelial-mesenchymal transition and poor prognosis in colorectal cancer

2016; Impact Journals LLC; Volume: 7; Issue: 21 Linguagem: Inglês

10.18632/oncotarget.8912

1949-2553

Christine Woischke, Cristina Blaj, Eva Marina Schmidt, Sebastian Lamprecht, Jutta Engel, Heiko Hermeking, Thomas Kirchner, David Horst,

Cancer-related Molecular Pathways

// Christine Woischke 1, * , Cristina Blaj 1, * , Eva Marina Schmidt 1, * , Sebastian Lamprecht 1 , Jutta Engel 2 , Heiko Hermeking 1, 3, 4 , Thomas Kirchner 1, 3, 4 , David Horst 1, 3, 4 1 Pathologisches Institut, Ludwig-Maximilians-Universität München, München, Germany 2 Tumorregister München, Institut für medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität München, München, Germany 3 German Cancer Consortium (DKTK), Heidelberg, Germany 4 German Cancer Research Center (DKFZ), Heidelberg, Germany * These authors have contributed equally to this work Correspondence to: David Horst, email: david.horst@med.uni-muenchen.de Keywords: CYB5R1, colorectal cancer, EMT, survival, drug metabolism Received: October 13, 2015 Accepted: April 10, 2016 Published: April 22, 2016 ABSTRACT Colorectal cancers show significant tumor cell heterogeneity within the same core genetic background. Epithelial-mesenchymal transition (EMT) is an important functional aspect of this heterogeneity and hallmark of colorectal cancer progression. Here, we identify CYB5R1, an enzyme involved in oxidative stress protection and drug metabolism, as an indicator of EMT in colon cancer. We demonstrate high CYB5R1 expression in colorectal cancer cells undergoing EMT at the infiltrative tumor edge and reveal an extraordinarily strong association of CYB5R1 expression with two core EMT gene expression signatures in a large independent colon cancer data set from The Cancer Genome Atlas (TCGA). Furthermore, we demonstrate that CYB5R1 is required for an infiltrative tumor cell phenotype, and robustly linked with poor prognosis in colorectal cancer. Our findings have important implications for colon cancer cells undergoing EMT and may be exploited for diagnostic and therapeutic purposes.