Mucosal Immunity and Tumor Biology of DMBT1

Deleted in Malignant Brain Tumours 1 (DMBT1) is a multifunctional glycoprotein that occupies a central position at the interface of innate mucosal defence and tumour suppression. Expressed on a range of mucosal surfaces—including the oral cavity, airways and gastrointestinal tract—DMBT1 binds microbial ligands through repeated scavenger receptor cysteine-rich (SRCR) domains and adjacent glycosylated regions. By agglutinating bacteria and modulating complement activation, it limits microbial invasion and shapes the composition of commensal communities. In parallel, DMBT1 influences epithelial homeostasis and repair through interactions with growth factors and inflammatory mediators, thereby balancing immune protection with tissue regeneration. Loss or down-regulation of DMBT1 has been documented in diverse malignancies, and its expression correlates inversely with tumour progression in breast, gastric and colorectal tissues. Genetic variants affecting SRCR copy number or regulatory polymorphisms further modulate both microbial binding and susceptibility to inflammatory and neoplastic disease. Together, these observations underscore DMBT1 as a pivotal pattern-recognition receptor whose structural and post-translational features mediate a dynamic cross-talk between mucosal immunosurveillance and tumour biology.

Research from Nature Portfolio

Recent studies have dissected the molecular requirements for DMBT1-mediated inhibition of bacterial motility, a key determinant of mucosal colonisation. Analysis of its N-terminal region revealed that intact SRCR arrays with native N-glycosylation are essential to block Pseudomonas aeruginosa twitching motility, whereas isolated peptide motifs or deglycosylated forms lack activity despite retaining pilus binding. These findings highlight a cooperative mechanism in which glycosylated inter-domain segments stabilise higher-order assemblies needed to impede microbial movement. The work advances understanding of how DMBT1’s structural complexity underpins its scavenger function and suggests routes to harness or mimic its anti-virulence properties at mucosal surfaces.

Mucosal Immunity and Tumor Biology of DMBT1 publication trend

The graph below shows the total number of articles in mucosal immunity and tumor biology of dmbt1 across all publications each year (not limited to Nature Index journals).

Technical terms

Scavenger receptor cysteine-rich (SRCR) domain: A ~110-amino-acid module characterised by conserved disulfide bonds; mediates ligand binding to microbes and host proteins.

Glycosylation: The enzymatic attachment of carbohydrate chains to specific amino acids, modulating protein folding, stability and ligand interactions.

Pilus-mediated twitching motility: Surface translocation of bacteria powered by extension and retraction of type IV pili, contributing to colonisation and biofilm formation.

Pattern recognition receptor: A germline-encoded protein that identifies conserved microbial structures, initiating innate immune responses.

References

1. Deleted in Malignant Brain Tumors-1 Protein (DMBT1): A Pattern Recognition Receptor with Multiple Binding Sites. International Journal of Molecular Sciences (2010).
2. SALSA: A Regulator of the Early Steps of Complement Activation on Mucosal Surfaces. Frontiers in Immunology (2016).
3. Salivary Agglutinin, Which Binds Streptococcus mutansand Helicobacter pylori, Is the Lung Scavenger Receptor Cysteine-rich Protein gp-340*. Journal of Biological Chemistry (2000).
4. Deleted in malignant brain tumors 1 (DMBT1) elicits increased VEGF and decreased IL-6 production in type II lung epithelial cells. BMC Pulmonary Medicine (2015).
5. DMBT1 expression is down-regulated in breast cancer. BMC Cancer (2004).
6. Intestinal DMBT1 Expression Is Modulated by Crohn’s Disease-Associated IL23R Variants and by a DMBT1 Variant Which Influences Binding of the Transcription Factors CREB1 and ATF-2. PLOS ONE (2013).
7. The scavenging capacity of DMBT1 is impaired by germline deletions. Immunogenetics (2017).
8. DMBT1 inhibition of Pseudomonas aeruginosa twitching motility involves its N-glycosylation and cannot be conferred by the Scavenger Receptor Cysteine-Rich bacteria-binding peptide domain. Scientific Reports (2019).
9. Structures of SALSA/DMBT1 SRCR domains reveal the conserved ligand-binding mechanism of the ancient SRCR fold. Life Science Alliance (2020).
10. Increased expression of deleted in malignant brain tumors ( DMBT1 ) gene in precancerous gastric lesions: Findings from human and animal studies. Oncotarget (2017).