Although most people don't think much of mucus, its important functions, such as lubricating the epithelia and protecting against infection, are undisputed. Recent findings, reported in the 1 March issue of Science, reveal a new function for this underappreciated substance — preventing the development of colorectal cancer.

A family of high-molecular-weight secreted glycoproteins known as mucins are a primary component of the mucus layer. To date, thirteen different mucins have been discovered (MUC1–13), and found to be expressed in different tissues. Alterations in mucin expression and glycosylation pattern have been observed in human colon cancer samples, and MUC2 — the most abundant gastrointestinal mucin — is reportedly downregulated in human colorectal carcinomas. Little is known, however, about MUC2 function at the molecular level.

To evaluate the role of MUC2 in tumorigenesis, Anna Velcich et al. created Muc2-null mice. Muc2 is highly expressed by the mucus-producing goblet cells of the intestine. The authors found that Muc2-null mice did not develop recognizable goblet cells in any region of the intestine, and were therefore defective in mucus production. Muc2-null mice are able to digest food and absorb nutrients, as they gained weight at the same rate as their heterozygous and wild-type littermates. But 65% of Muc2-null mice developed gastrointestinal tumours by the time they are 1 year old. These tumours were found in the small and large intestine and rectum, but not in the stomach, where Muc2 is not normally expressed.

So what is the function of Muc2 in the intestinal epithelium? Velcich et al. believe that Muc2 is involved in regulating cell proliferation and migration, as intestinal epithelial cells of Muc2-null mice had a higher proliferation:apoptosis ratio than those of wild-type epithelium, resulting in elongated crypts. Muc2-null epithelial cells also migrated faster in the intestinal mucosa than in wild-type cells — in mice injected with bromodeoxyuridine, labelled epithelial cells of Muc2-null mice migrated more rapidly to proximal regions of intestinal villi. Tumours that developed in Muc2-null cells overexpressed c-Myc, a known regulator of cell proliferation, so Muc2 might somehow regulate the expression of this oncogenic transcription factor.

Inactivation of Muc2 therefore causes intestinal tumour formation, and is also required for normal goblet-cell formation and mucus production. Further experiments are required to determine whether tumour development in these mice is due to the absence of the lubricating effect of mucus, or alterations in the epithelial-cell signalling pathways that regulate cell proliferation.