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Updated: Dec 3, 2025

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Transmembrane and Immunoglobulin Domain Containing 1, a Putative Tumor Suppressor, Induces G2/M Cell Cycle Checkpoint

Kyle O C De La Cena1, Rachel X-Y Ho1, Razie Amraei1

  • 1Department of Pathology, School of Medicine, Boston University Medical Campus, Boston, Massachusetts.

The American Journal of Pathology
|November 1, 2020
PubMed

Insights

The cell adhesion molecule TMIGD1 acts as a tumor suppressor in colorectal cancer (CRC). Loss of TMIGD1 promotes adenoma formation and impairs intestinal epithelium, highlighting its crucial role in CRC pathogenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gastroenterology

Background:

  • Colorectal cancer (CRC) remains a significant cause of cancer mortality.
  • The complete molecular mechanisms driving CRC tumorigenesis are not fully elucidated.
  • Understanding novel genetic and epigenetic factors is crucial for CRC research.

Purpose of the Study:

  • To investigate the role of cell adhesion molecule TMIGD1 in colorectal cancer.
  • To determine the molecular mechanisms by which TMIGD1 influences intestinal epithelium and tumor development.
  • To evaluate TMIGD1 as a potential therapeutic target for CRC.

Main Methods:

  • Generation and analysis of TMIGD1 knockout mice.
  • Assessment of intestinal epithelium morphology, polarity, and maturation.
  • Evaluation of cell proliferation, migration, and cell cycle progression.
  • Analysis of p21CIP1 and p27KIP1 expression.
  • Correlation analysis of TMIGD1 expression with human CRC patient data.

Main Results:

  • TMIGD1 is highly expressed in normal intestinal epithelial cells but downregulated in sporadic human CRC.
  • Loss of TMIGD1 in mice led to the development of intestinal adenomas.
  • TMIGD1 deficiency impaired intestinal brush border membrane, junctional polarity, and maturation.
  • TMIGD1 inhibits tumor cell proliferation and migration, arresting the cell cycle at G2/M phase.
  • Downregulation of TMIGD1 correlated with poor patient survival.

Conclusions:

  • TMIGD1 functions as a novel tumor suppressor gene in colorectal cancer.
  • TMIGD1 plays a critical role in maintaining intestinal epithelial integrity and function.
  • TMIGD1 represents a potential therapeutic target for colorectal cancer treatment.

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