Title
MTG16 is a Tumor Suppressor in Colitis-Associated Carcinoma
Funding Source
National Institutes of Health, Office of Medical Research, Department of Veterans Affairs, American Cancer Society
Grant Number
5T32DK007673 (EMM), K08DK080221, R01DK099204 (CSW), P50CA095103 (MKW), 1F30DK096718 (BP), 1F31CA167920 (CWB), T32GM07347 (BP), R01AT004821 (KTW), K23DK094832 (MJR), P30DK058404, UL1TR000445, 1I01BX001426 (CSW), 2I01BX001453 (KTW), and 1IK2BX002126 (LAC), RSG 116552 (CSW
Department
Department of Biology
Document Type
Article
Publication Date
8-17-2017
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
Recommended Citation
McDonough, E. M.; Barrett, Caitlyn W.; Parang, B.; Mittal, Mukul K.; Smith, J. J.; Bradley, Amber M.; Choksi, Y. A.; Coburn, L. A.; Short, S. P.; Thompson, J. J.; Zhang, B.; and Poindexter Toliver, Shenika, "MTG16 is a Tumor Suppressor in Colitis-Associated Carcinoma" (2017). Faculty and Staff Publications. 189.
https://digitalcommons.xula.edu/fac_pub/189
Comments
DOI: 10.1172/jci.insight.78210
PubMed ID: 28814670
Acknowledgment
This work was supported by the NIH grants 5T32DK007673 (EMM), K08DK080221, R01DK099204 (CSW), P50CA095103 (MKW), 1F30DK096718 (BP), 1F31CA167920 (CWB), T32GM07347 (BP), R01AT004821 (KTW), K23DK094832 (MJR), P30DK058404 (Vanderbilt Digestive Disease Research Center), and UL1TR000445 (Vanderbilt CTSA); Merit Review Grants from the Office of Medical Research, Department of Veterans Affairs 1I01BX001426 (CSW), 2I01BX001453 (KTW), and 1IK2BX002126 (LAC); and the American Cancer Society ACS-RSG 116552 (CSW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.