Journal article
MTG16 is a tumor suppressor in colitis-associated carcinoma
JCI insight, Vol.2(16), e78210
08/17/2017
DOI: 10.1172/jci.insight.78210
PMCID: PMC5621889
PMID: 28814670
Abstract
MTG16 is a member of the myeloid translocation gene (MTG) family of transcriptional corepressors. While MTGs were originally identified in chromosomal translocations in acute myeloid leukemia, recent studies have uncovered a role in intestinal biology. For example,
Mtg16
–/–
mice have increased intestinal proliferation and are more sensitive to intestinal injury in colitis models. MTG16 is also underexpressed in patients with moderate/severe ulcerative colitis. Based on these findings, we postulated that MTG16 might protect against colitis-associated carcinogenesis. MTG16 was downregulated at the protein and RNA levels in patients with inflammatory bowel disease and in those with colitis-associated carcinoma.
Mtg16
–/–
mice subjected to inflammatory carcinogenesis modeling exhibited worse colitis and increased tumor multiplicity and size. Loss of MTG16 also increased severity of dysplasia, apoptosis, proliferation, DNA damage, and WNT signaling. Moreover, transplantation of WT marrow into
Mtg16
–/–
mice failed to rescue the
Mtg16
–/–
protumorigenic phenotypes, indicating an epithelium-specific role for MTG16. While MTG dysfunction is widely appreciated in hematopoietic malignancies, the role of this gene family in epithelial homeostasis, and in colon cancer, was unrealized. This report identifies MTG16 as an important modulator of colitis and tumor development in inflammatory carcinogenesis.
Myeloid translocation gene 16 is a modulator of colitis and tumor development in colitis-associated carcinoma.
Details
- Title: Subtitle
- MTG16 is a tumor suppressor in colitis-associated carcinoma
- Creators
- Elizabeth M. McDonough - Stanford University School of MedicineCaitlyn W. Barrett - Stanford University School of MedicineBobak Parang - Stanford University School of MedicineMukul K. Mittal - Stanford University School of MedicineJ. Joshua Smith - Stanford University School of MedicineAmber M. Bradley - Stanford University School of MedicineYash A. Choksi - Stanford University School of MedicineLori A. Coburn - Stanford University School of MedicineSarah P. Short - Stanford University School of MedicineJoshua J. Thompson - Stanford University School of MedicineBaolin Zhang - Stanford University School of MedicineShenika V. Poindexter - Stanford University School of MedicineMelissa A. Fischer - Stanford University School of MedicineXi Chen - University of MiamiJiang Li - Stanford UniversityFrank L. Revetta - Vanderbilt University Medical CenterRishi Naik - Stanford University School of MedicineM. Kay Washington - Stanford University School of MedicineMichael J. Rosen - Stanford University School of MedicineScott W. Hiebert - Vanderbilt University Medical CenterKeith T. Wilson - Stanford University School of MedicineChristopher S. Williams - Stanford University School of Medicine
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.2(16), e78210
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/jci.insight.78210
- PMID
- 28814670
- PMCID
- PMC5621889
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Language
- English
- Date published
- 08/17/2017
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984420934702771
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