TitleReciprocal regulation of BMF and BIRC5 (Survivin) linked to Eomes overexpression in colorectal cancer.
Publication TypeJournal Article
Year of Publication2016
AuthorsWang, R, Kang, Y, Löhr, CV, Fischer, KA, C Bradford, S, Johnson, G, Dashwood, WMohaiza, Williams, DE, Ho, E, Dashwood, RH
JournalCancer Lett
Volume381
Issue2
Pagination341-8
Date Published2016 10 28
ISSN1872-7980
KeywordsAdaptor Proteins, Signal Transducing, Adenocarcinoma, Animals, Antineoplastic Agents, Apoptosis, Cell Line, Tumor, Cell Survival, Colonic Neoplasms, G2 Phase Cell Cycle Checkpoints, Gene Expression Regulation, Neoplastic, Humans, Inhibitor of Apoptosis Proteins, Kaplan-Meier Estimate, Male, Microtubule-Associated Proteins, Neoplasm Staging, Rats, Inbred F344, RNA Interference, Signal Transduction, Staurosporine, Survival Analysis, Survivin, T-Box Domain Proteins, Time Factors, Transfection, Up-Regulation
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.

DOI10.1016/j.canlet.2016.08.008
Alternate JournalCancer Lett.
PubMed ID27539959
PubMed Central IDPMC5035225
Grant ListP01 CA090890 / CA / NCI NIH HHS / United States
P30 ES000210 / ES / NIEHS NIH HHS / United States
P30 ES023512 / ES / NIEHS NIH HHS / United States
R01 CA122959 / CA / NCI NIH HHS / United States