Mouse Models of Colorectal Cancer Mechanisms

Mouse models of colorectal cancer have been instrumental in elucidating the genetic and cellular pathways that drive tumour initiation, progression and metastasis. Chemically induced systems, using agents such as azoxymethane or dimethylhydrazine, mimic sporadic mutagenesis and enable studies of early neoplastic lesions in a controlled setting. Genetically engineered mouse models (GEMMs), notably those harbouring mutations in the adenomatous polyposis coli (Apc) gene, recapitulate key features of human familial and sporadic colorectal cancer. The ApcMin/+ model has provided a cornerstone for exploring Wnt–β-catenin signalling, while more recent conditional alleles of Kras, Tp53 and Tgfbr1 have shed light on cooperative oncogenic events and the suppressive influence of TGFβ. Organoid-based approaches derived from murine intestinal crypts now permit high-resolution dissection of lineage plasticity and microenvironmental crosstalk. Inflammation-driven protocols combining dextran sodium sulfate with genetic predisposition further reveal how immune cells, cytokine networks and stromal interactions promote tumourigenesis. Together, these platforms have defined molecular thresholds for β-catenin activation, identified the role of epithelial–mesenchymal transition, and established preclinical avenues for testing targeted therapies and immunomodulatory strategies.

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Mouse Models of Colorectal Cancer Mechanisms publication trend

The graph below shows the total number of articles in mouse models of colorectal cancer mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Genetically engineered mouse model (GEMM): A mouse line modified to carry specific human cancer-associated gene alterations for in vivo study of tumour biology.

ApcMin/+ mouse: A widely used GEMM harbouring a truncating mutation in the Apc gene that leads to multiple intestinal adenomas driven by Wnt pathway deregulation.

Dextran sodium sulfate (DSS): A chemical irritant added to drinking water to induce colitis in mice, modelling inflammation-associated colorectal cancer.

Organoid: A three-dimensional culture of primary epithelial cells that self-organises into crypt-like structures, enabling mechanistic and therapeutic studies ex vivo.

Tumour microenvironment (TME): The complex milieu of stromal cells, immune infiltrates, extracellular matrix and signalling molecules surrounding a developing tumour.

References

1. Overview of research progress and application of experimental models of colorectal cancer. Frontiers in Pharmacology (2023).
2. Integrin-linked kinase expression in myeloid cells promotes colon tumorigenesis. Frontiers in Immunology (2023).
3. TGFβ pathway limits dedifferentiation following WNT and MAPK pathway activation to suppress intestinal tumourigenesis. Cell Death & Differentiation (2017).
4. Genetic Dissection of Differential Signaling Threshold Requirements for the Wnt/β-Catenin Pathway In Vivo. PLOS Genetics (2010).