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In vitro Organoid Culture of Primary Mouse Colon Tumors
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Keratins in colorectal epithelial function and disease.

Debabrata Majumdar1, James P Tiernan, Alan J Lobo

  • 1Molecular Gastroenterology Research Group, Academic Unit of Surgical Oncology, Department of Oncology, The Medical School, University of Sheffield, Sheffield, UK.

International Journal of Experimental Pathology
|September 15, 2012
PubMed
Summary

Keratins are crucial for intestinal health, maintaining epithelial integrity and function. Alterations in keratin expression are linked to inflammatory bowel disease and colorectal cancers, highlighting their role as disease biomarkers.

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Area of Science:

  • Cell Biology
  • Gastroenterology
  • Oncology

Background:

  • Keratins (K) are intermediate filament proteins essential for cytoskeleton structure.
  • Intestinal epithelial keratins (K8, K18, K19) provide strength and regulate ion transport.
  • Keratin dynamics are modulated by post-translational modifications, impacting solubility and stability.

Purpose of the Study:

  • To review the biology and physiological functions of keratins.
  • To explore alterations in keratin expression in inflammatory bowel disease (IBD) and colorectal cancers (CRCs).
  • To discuss the role of keratins as potential biomarkers for gastrointestinal diseases.

Main Methods:

  • Literature review focusing on keratin biology, function, and disease association.
  • Analysis of studies investigating keratin expression in IBD and CRC.
  • Examination of keratin post-translational modifications and their impact.

Main Results:

  • Keratin null mice develop colitis, indicating keratin's role in intestinal homeostasis.
  • Abnormal keratin expression (e.g., K7, K20) is associated with colitis-associated dysplasia and CRCs.
  • Caspase-cleaved keratin 18 (M30) in serum serves as a marker for CRC progression and therapy response.

Conclusions:

  • Keratins are vital for normal gastrointestinal epithelium function.
  • Keratin dysregulation is implicated in IBD and CRC pathogenesis.
  • Keratins and their fragments show promise as diagnostic and prognostic markers for colorectal diseases.