Myeloid translocation genes differentially regulate colorectal cancer programs

Bobak Parang; Amber M. Bradley; Mukul K. Mittal; Sarah P. Short; Joshua J. Thompson; Caitlyn W. Barrett; Rishi D. Naik; Anthony J. Bilotta; Mary K. Washington; Frank L. Revetta; Jesse J. Smith; Xi Chen; Keith T. Wilson; Scott W. Hiebert; Christopher S. Williams

doi:10.1038/onc.2016.167

Back

Myeloid translocation genes differentially regulate colorectal cancer programs

Journal article

Open access

Peer reviewed

Myeloid translocation genes differentially regulate colorectal cancer programs

Bobak Parang, Amber M. Bradley, Mukul K. Mittal, Sarah P. Short, Joshua J. Thompson, Caitlyn W. Barrett, Rishi D. Naik, Anthony J. Bilotta, Mary K. Washington, Frank L. Revetta, …

Oncogene, Vol.35(49), pp.6341-6349

12/08/2016

DOI: 10.1038/onc.2016.167

PMCID: PMC5140770

PMID: 27270437

Files and links (1)

url

https://doi.org/10.1038/onc.2016.167View

Published (Version of record) Open Access

Abstract

Myeloid translocation genes (MTGs), originally identified as chromosomal translocations in acute myelogenous leukemia, are transcriptional corepressors that regulate hematopoietic stem cell programs. Analysis of The Cancer Genome Atlas (TCGA) database revealed that MTGs were mutated in epithelial malignancy and suggested that loss of function might promote tumorigenesis. Genetic deletion of MTGR1 and MTG16 in the mouse has revealed unexpected and unique roles within the intestinal epithelium. Mtgr1 −/− mice have progressive depletion of all intestinal secretory cells, and Mtg16 −/− mice have a decrease in goblet cells. Furthermore, both Mtgr1 −/− and Mtg16 −/− mice have increased intestinal epithelial cell proliferation. We thus hypothesized that loss of MTGR1 or MTG16 would modify Apc 1638/+ -dependent intestinal tumorigenesis. Mtgr1 −/− mice, but not Mtg16 −/− mice, had a 10-fold increase in tumor multiplicity. This was associated with more advanced dysplasia, including progression to invasive adenocarcinoma, and augmented intratumoral proliferation. Analysis of ChIP-seq datasets for MTGR1 and MTG16 targets indicated that MTGR1 can regulate Wnt and Notch signaling. In support of this, immunohistochemistry and gene expression analysis revealed that both Wnt and Notch signaling pathways were hyperactive in Mtgr1 −/− tumors. Furthermore, in human colorectal cancer (CRC) samples MTGR1 was downregulated at both the transcript and protein level. Overall our data indicates that MTGR1 has a context dependent effect on intestinal tumorigenesis.

Apc1638

Colon cancer

MTG16

MTGR1

Details

Title: Subtitle: Myeloid translocation genes differentially regulate colorectal cancer programs
Creators: Bobak Parang - Vanderbilt University
Amber M. Bradley - Department of Medicine, Division of Gastroenterology Department of Cancer Biology Department of Pathology, Microbiology, and Immunology Department of Surgery, Division of Surgical Oncology Department of Biostatistics Department of Biochemistry Vanderbilt Ingram Cancer Center Veterans Affairs Tennessee Valley Health Care System, Nashville, TN. USA
Mukul K. Mittal - Department of Medicine, Division of Gastroenterology Department of Cancer Biology Department of Pathology, Microbiology, and Immunology Department of Surgery, Division of Surgical Oncology Department of Biostatistics Department of Biochemistry Vanderbilt Ingram Cancer Center Veterans Affairs Tennessee Valley Health Care System, Nashville, TN. USA
Sarah P. Short - Vanderbilt University
Joshua J. Thompson - Department of Medicine, Division of Gastroenterology Department of Cancer Biology Department of Pathology, Microbiology, and Immunology Department of Surgery, Division of Surgical Oncology Department of Biostatistics Department of Biochemistry Vanderbilt Ingram Cancer Center Veterans Affairs Tennessee Valley Health Care System, Nashville, TN. USA
Caitlyn W. Barrett - Department of Medicine, Division of Gastroenterology Department of Cancer Biology Department of Pathology, Microbiology, and Immunology Department of Surgery, Division of Surgical Oncology Department of Biostatistics Department of Biochemistry Vanderbilt Ingram Cancer Center Veterans Affairs Tennessee Valley Health Care System, Nashville, TN. USA
Rishi D. Naik - Vanderbilt University
Anthony J. Bilotta - Vanderbilt University
Mary K. Washington - Department of Medicine, Division of Gastroenterology Department of Cancer Biology Department of Pathology, Microbiology, and Immunology Department of Surgery, Division of Surgical Oncology Department of Biostatistics Department of Biochemistry Vanderbilt Ingram Cancer Center Veterans Affairs Tennessee Valley Health Care System, Nashville, TN. USA
Frank L. Revetta - Nashville Oncology Associates
Jesse J. Smith - Department of Medicine, Division of Gastroenterology Department of Cancer Biology Department of Pathology, Microbiology, and Immunology Department of Surgery, Division of Surgical Oncology Department of Biostatistics Department of Biochemistry Vanderbilt Ingram Cancer Center Veterans Affairs Tennessee Valley Health Care System, Nashville, TN. USA
Xi Chen - Department of Biostatistics, Nashville, USA
Keith T. Wilson - Department of Medicine, Division of Gastroenterology Department of Cancer Biology Department of Pathology, Microbiology, and Immunology Department of Surgery, Division of Surgical Oncology Department of Biostatistics Department of Biochemistry Vanderbilt Ingram Cancer Center Veterans Affairs Tennessee Valley Health Care System, Nashville, TN. USA
Scott W. Hiebert - Vanderbilt University
Christopher S. Williams - Department of Medicine, Division of Gastroenterology Department of Cancer Biology Department of Pathology, Microbiology, and Immunology Department of Surgery, Division of Surgical Oncology Department of Biostatistics Department of Biochemistry Vanderbilt Ingram Cancer Center Veterans Affairs Tennessee Valley Health Care System, Nashville, TN. USA
Resource Type: Journal article
Publication Details: Oncogene, Vol.35(49), pp.6341-6349
DOI: 10.1038/onc.2016.167
PMID: 27270437
PMCID: PMC5140770
NLM abbreviation: Oncogene
ISSN: 0950-9232
eISSN: 1476-5594
Language: English
Date published: 12/08/2016
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984420840802771

Metrics

11 Record Views

11 Times Cited - Web of Science