title: Reciprocal regulation of BMF and BIRC5 (Survivin) linked to Eomes overexpression in colorectal cancer.
abstract: Eomesodermin (Eomes) is a T-box transcription factor that has been implicated in the etiology of colorectal cancer and other human malignancies. We screened a panel of human primary colon cancers and patient-matched controls (n = 30) and detected Eomes overexpression at the mRNA and protein level. Similar results were obtained in a panel of rat colon tumors and adjacent normal-looking colonic mucosa (n = 24). In human colon cancer cells, forced overexpression of Eomes enhanced cell viability and protected against staurosporine-induced apoptosis. On the other hand, knocking down Eomes resulted in reduced cell viability, G2/M cell cycle arrest, and apoptosis induction. The apoptotic mechanism centered on the reciprocal downregulation of anti-apoptotic BIRC5 (Survivin) and upregulation of proapoptotic Bcl-2 modifying factor (BMF). In patients with colorectal cancer, high EOMES expression (n = 95) was associated with poor overall survival compared with individuals exhibiting low EOMES levels (n = 80). We conclude from the current investigation, and prior literature, that Eomes has a divergent role in cancer development, with evidence for tumor suppressor and oncogenic functions, depending on stage and tissue context. Further studies are warranted on the apoptotic mechanisms linked to the reciprocal regulation of BMF and BIRC5 in human colorectal cancers characterized by Eomes overexpression.
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kang
authors.affiliation: College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
authors.forename: Christiane V
authors.initials: CV
authors.lastname: Löhr
authors.affiliation: College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
authors.forename: Kay A
authors.initials: KA
authors.lastname: Fischer
authors.affiliation: Department of Environmental & Molecular Toxicology, Oregon State University, Corvallis, OR, USA.
authors.forename: C Samuel
authors.initials: CS
authors.lastname: Bradford
authors.affiliation: Center for Epigenetics & Disease Prevention, Texas A&M University Health Science Center, Houston, TX, USA.
authors.forename: Gavin
authors.initials: G
authors.lastname: Johnson
authors.affiliation: Center for Epigenetics & Disease Prevention, Texas A&M University Health Science Center, Houston, TX, USA.
authors.forename: Wan Mohaiza
authors.initials: WM
authors.lastname: Dashwood
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR, USA; Department of Environmental & Molecular Toxicology, Oregon State University, Corvallis, OR, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Williams
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR, USA; Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Ho
authors.affiliation: Center for Epigenetics & Disease Prevention, Texas A&M University Health Science Center, Houston, TX, USA; Department of Nutrition and Food Science, Texas A&M University, College Station, TX, USA; Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University, College Station, TX, USA; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: rdashwood@ibt.tamhsc.edu.
authors.forename: Roderick H
authors.initials: RH
authors.lastname: Dashwood
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D034622:RNA Interference; D011916:Rats, Inbred F344; D015398:Signal Transduction; D019311:Staurosporine / Q000494:pharmacology; D016019:Survival Analysis; D000077022:Survivin; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; C486655:BMF protein, human; C516989:Birc5 protein, rat; C486656:Bmf protein, rat; C491199:EOMES protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin; D020825:T-Box Domain Proteins; C000621541:eomes protein, rat; D019311:Staurosporine
keywords: Apoptosis; Bcl-2 modifying factor; Caspase; Heterocyclic amine; TCGA