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Transmembrane and Immunoglobulin Domain Containing 1, a Putative Tumor Suppressor, Induces G2/M Cell Cycle Checkpoint Arrest in Colon Cancer Cells
- Source :
- Am J Pathol
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Colorectal cancer (CRC) is a leading nonfamilial cause of cancer mortality among men and women. Although various genetic and epigenetic mechanisms have been identified, the full molecular mechanisms deriving CRC tumorigenesis are not fully understood. This study demonstrates that cell adhesion molecule transmembrane and immunoglobulin domain containing 1 (TMIGD1) are highly expressed in mouse and human normal intestinal epithelial cells. TMIGD1 knockout mice were developed, and the loss of TMIGD1 in mice was shown to result in the development of adenomas in small intestine and colon. In addition, the loss of TMIGD1 significantly impaired intestinal epithelium brush border membrane, junctional polarity, and maturation. Mechanistically, TMIGD1 inhibits tumor cell proliferation and cell migration, arrests cell cycle at the G2/M phase, and induces expression of p(21CIP1) (cyclin-dependent kinase inhibitor 1), and p(27KIP1) (cyclin-dependent kinase inhibitor 1B) expression, key cell cycle inhibitor proteins involved in the regulation of the cell cycle. Moreover, TMIGD1 is shown to be progressively down-regulated in sporadic human CRC, and its downregulation correlates with poor overall survival. The findings herein identify TMIGD1 as a novel tumor suppressor gene and provide new insights into the pathogenesis of colorectal cancer and a novel potential therapeutic target.
- Subjects :
- Adenoma
0301 basic medicine
Tumor suppressor gene
Colorectal cancer
Biology
medicine.disease_cause
Pathology and Forensic Medicine
Mice
03 medical and health sciences
0302 clinical medicine
Cell Movement
medicine
Animals
Humans
Genes, Tumor Suppressor
Cell Proliferation
Mice, Knockout
Membrane Glycoproteins
Kinase
Cell adhesion molecule
Tumor Suppressor Proteins
Regular Article
Cell migration
Cell Cycle Checkpoints
Cell cycle
medicine.disease
Intestinal epithelium
G2 Phase Cell Cycle Checkpoints
Cell Transformation, Neoplastic
030104 developmental biology
030220 oncology & carcinogenesis
Colonic Neoplasms
Cancer research
Carcinogenesis
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 191
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....c5bb237d8ab9ca60504f89ed7ef6dae8