Trends in Molecular Medicine
ReviewMicrobe–MUC1 Crosstalk in Cancer-Associated Infections
Section snippets
Infection-Induced Cancer
Diverse modifiable risk factors are associated with cancer incidence, such as an imbalanced diet and exposure to carcinogens and infectious agents including viruses, bacteria, and parasites. The human body harbors millions of bacteria, viruses, and fungi that are unique to each individual and make up their microbiome. This microbiome can regulate cancer susceptibility, progression, and response to therapy [1, 2, 3]. Infectious diseases represent the third leading cause of cancer incidence (//www.wikiwand.com/en/Cancer_prevention#/preventable_causes_of_cancer
MUC1 is a Gatekeeper at the Mucosal Barrier
Mucins are highly glycosylated in normal tissues but are overexpressed and aberrantly glycosylated in tumors [7]. In healthy tissues, mucins form a mucosal barrier and sense bacterial ligands and mucosal cell damage. Mucins further relay this information by activating immunomodulatory pathways, thus initiating differentiation or apoptosis of cells when required [8]. It appears that cancer cells use altered mucins to evade cell death signals and immune cell killing. The question is whether
Anti- versus Proinflammatory Roles of MUC1 during Bacterial Infection
Bacteria have been largely neglected as cancer-causing factors compared with viruses, and only a few bacterial infections are known to be associated with cancer development, Bacteria may contribute to cancer development through inflammation, secretion of toxins and metabolites that damage DNA, and/or manipulation of host signaling pathways during infection [19,20]. Two well-known bacterial infections that are associated with cancer development are (i) Helicobacter pylori, that is associated
Epstein–Barr Virus and MUC1
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is commonly associated with nasopharyngeal carcinoma (NPC), Hodgkin's lymphoma, Burkitt's lymphoma, natural killer (NK)/T cell lymphomas, and some gastric carcinomas [64,65]. EBV-associated NPC has highly metastatic characteristics and poor prognosis. As a key effector in EBV-driven malignancies, EBV latent membrane protein 1 (LMP1) displays oncogenic properties in epithelial cell lines and confirms that EBV infection contributes
Parasites
Common parasitic infections that can lead to cancer include Schistosoma haematobium, the only blood fluke that infects the urinary tract, and Opisthorchis viverrini, a liver fluke that infects the bile duct, causing opisthorchiasis. Schistosoma infection causes urinary schistosomiasis, and is the second leading cause of squamous cell carcinoma of the bladder, the first being tobacco smoking [78,79]. Opisthorchis viverrini increases the risk of cholangiocarcinoma (CC), a cancer of the bile ducts
Concluding Remarks
Studying microbe–MUC1 crosstalk in different infection-induced cancers may open avenues for further research (Figure 3, Key Figure). These interactions modulate local and systemic inflammatory responses, oncogenic signaling, and tumor progression. The concept of cancer-immunoediting states that the process of cancer development comprises three phases that collectively denote the three 'E's of cancer immunoediting: elimination, equilibrium, and escape (Box 1) [82].
In infection-induced cancers
Acknowledgments
We would like to acknowledge Dr Timothy Erick for reviewing the manuscript for clarity.
Glossary
- Elimination
- a phase in the cancer immunoediting process in which the immune system successfully eliminates the tumor cells.
- Equilibrium
- a cancer immunoediting phase in which the immune system is engaged in a constant fight with the tumor cells; this is also a period of Darwinian selection which selects for immune-resistant tumor cells.
- Escape
- a cancer immunoediting phase in which the tumor cells have already evaded the immune responses and established themselves.
- Glycome
- the entire complement of
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