CYB5R1 links epithelial-mesenchymal transition and poor prognosis in colorectal cancer.
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.
Pathologisches Institut, Ludwig-Maximilians-Universität München, München, Germany.
Christine
C
Woischke
Pathologisches Institut, Ludwig-Maximilians-Universität München, München, Germany.
Cristina
C
Blaj
Pathologisches Institut, Ludwig-Maximilians-Universität München, München, Germany.
Eva Marina
EM
Schmidt
Pathologisches Institut, Ludwig-Maximilians-Universität München, München, Germany.
Sebastian
S
Lamprecht
Tumorregister München, Institut für medizinische Informationsverarbeitung, Biometrie und Epidemiologie, Ludwig-Maximilians-Universität München, München, Germany.
Jutta
J
Engel
Pathologisches Institut, Ludwig-Maximilians-Universität München, München, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
Heiko
H
Hermeking
Pathologisches Institut, Ludwig-Maximilians-Universität München, München, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
Thomas
T
Kirchner
Pathologisches Institut, Ludwig-Maximilians-Universität München, München, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
David
D
Horst
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D042966:Cytochrome-B(5) Reductase / Q000235:genetics* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D034622:RNA Interference; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C000625630:CYB5R1 protein, human; D042966:Cytochrome-B(5) Reductase
CYB5R1; EMT; colorectal cancer; drug metabolism; survival