CYB5R1 links epithelial-mesenchymal transition and poor prognosis in colorectal cancer
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Christine Woischke1,*, Cristina Blaj1,*, Eva Marina Schmidt1,*, Sebastian Lamprecht1, Jutta Engel2, Heiko Hermeking1,3,4, Thomas Kirchner1,3,4, David Horst1,3,4
1Pathologisches Institut, Ludwig-Maximilians-Universität München, München, Germany
2Tumorregister München, Institut für medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität München, München, Germany
3German Cancer Consortium (DKTK), Heidelberg, Germany
4German Cancer Research Center (DKFZ), Heidelberg, Germany
*These authors have contributed equally to this work
David Horst, email: [email protected]
Keywords: CYB5R1, colorectal cancer, EMT, survival, drug metabolism
Received: October 13, 2015 Accepted: April 10, 2016 Published: April 22, 2016
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.
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