MTG16 is a tumor suppressor in colitis-associated carcinoma

Elizabeth M. McDonough, Caitlyn W. Barrett, Bobak Parang, Mukul K. Mittal, J. Joshua Smith, Amber M. Bradley, Yash A. Choksi, Lori A. Coburn, Sarah P. Short, Joshua J. Thompson, Baolin Zhang, Shenika V. Poindexter, Melissa A. Fischer, Xi Chen, Jiang Li, Frank L. Revetta, Rishi Naik, M. Kay Washington, Michael J. Rosen, Scott W. Hiebert & 2 others Keith T. Wilson, Christopher S. Williams

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
JournalJCI insight
Volume2
Issue number16
DOIs
StatePublished - Aug 17 2017

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Colitis
Carcinoma
Carcinogenesis
Neoplasms
Genes
Co-Repressor Proteins
Genetic Translocation
Hematologic Neoplasms
Ulcerative Colitis
Inflammatory Bowel Diseases
Acute Myeloid Leukemia
Colonic Neoplasms
DNA Damage
Homeostasis
Down-Regulation
Epithelium
Transplantation
Bone Marrow
RNA
Apoptosis

Keywords

  • Gastroenterology
  • Genetics
  • Inflammation
  • Oncology

Cite this

McDonough, E. M., Barrett, C. W., Parang, B., Mittal, M. K., Smith, J. J., Bradley, A. M., ... Williams, C. S. (2017). MTG16 is a tumor suppressor in colitis-associated carcinoma. JCI insight, 2(16). https://doi.org/10.1172/jci.insight.78210

MTG16 is a tumor suppressor in colitis-associated carcinoma. / McDonough, Elizabeth M.; Barrett, Caitlyn W.; Parang, Bobak; Mittal, Mukul K.; Smith, J. Joshua; Bradley, Amber M.; Choksi, Yash A.; Coburn, Lori A.; Short, Sarah P.; Thompson, Joshua J.; Zhang, Baolin; Poindexter, Shenika V.; Fischer, Melissa A.; Chen, Xi; Li, Jiang; Revetta, Frank L.; Naik, Rishi; Washington, M. Kay; Rosen, Michael J.; Hiebert, Scott W.; Wilson, Keith T.; Williams, Christopher S.

In: JCI insight, Vol. 2, No. 16, 17.08.2017.

Research output: Contribution to journalArticle

McDonough, EM, Barrett, CW, Parang, B, Mittal, MK, Smith, JJ, Bradley, AM, Choksi, YA, Coburn, LA, Short, SP, Thompson, JJ, Zhang, B, Poindexter, SV, Fischer, MA, Chen, X, Li, J, Revetta, FL, Naik, R, Washington, MK, Rosen, MJ, Hiebert, SW, Wilson, KT & Williams, CS 2017, 'MTG16 is a tumor suppressor in colitis-associated carcinoma', JCI insight, vol. 2, no. 16. https://doi.org/10.1172/jci.insight.78210
McDonough EM, Barrett CW, Parang B, Mittal MK, Smith JJ, Bradley AM et al. MTG16 is a tumor suppressor in colitis-associated carcinoma. JCI insight. 2017 Aug 17;2(16). https://doi.org/10.1172/jci.insight.78210
McDonough, Elizabeth M. ; Barrett, Caitlyn W. ; Parang, Bobak ; Mittal, Mukul K. ; Smith, J. Joshua ; Bradley, Amber M. ; Choksi, Yash A. ; Coburn, Lori A. ; Short, Sarah P. ; Thompson, Joshua J. ; Zhang, Baolin ; Poindexter, Shenika V. ; Fischer, Melissa A. ; Chen, Xi ; Li, Jiang ; Revetta, Frank L. ; Naik, Rishi ; Washington, M. Kay ; Rosen, Michael J. ; Hiebert, Scott W. ; Wilson, Keith T. ; Williams, Christopher S. / MTG16 is a tumor suppressor in colitis-associated carcinoma. In: JCI insight. 2017 ; Vol. 2, No. 16.
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AU - Bradley, Amber M.

AU - Choksi, Yash A.

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AU - Williams, Christopher S.

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