Keratins are the largest subgroup of
intermediate filament proteins, which are an important constituent of the cellular cytoskeleton. The principally expressed
keratins (K) of the intestinal epithelium are K8,
K18 and K19. The specific
keratin profile of a particular epithelium provides it with strength and integrity. In the colon,
keratins have been shown to regulate
electrolyte transport, likely by targeting ion transporters to their correct location in the colonocytes.
Keratins are highly dynamic and are subject to post-translational modifications including phosphorylation, acetylation and glycosylation. These affect the filament dynamics and hence solubility of
keratins and may contribute to protection against degradation.
Keratin null mice (K8(-/-) ) develop
colitis, and abnormal
keratin mutations have been shown to be associated with
inflammatory bowel disease (IBD). Abnormal expression of K7 and K20 has been noted in
colitis-associated dysplasia and
cancers. In sporadic
colorectal cancers (
CRCs) may be useful in predicting tumour prognosis; a low K20 expression is noted in
CRCs with high
microsatellite instability; and
keratins have been noted as dysregulated in peri-adenomatous fields.
Caspase-cleaved fragment of
K18 (M30) in the serum of patients with CRC has been used as a marker of
cancer load and to assess response to
therapy. These data suggest an emerging importance of
keratins in maintaining normal function of the gastrointestinal epithelium as well as being a marker of various colorectal diseases. This review will primarily focus on the biology of these
proteins, physiological functions and alterations in IBD and
CRCs.