Adenomatous Polyposis Coli Role in Colorectal Cancer Dynamics

Adenomatous Polyposis Coli (APC) is a multifunctional tumour suppressor whose inactivation represents one of the earliest and most frequent events in colorectal cancer (CRC) pathogenesis. In healthy intestinal epithelium, APC regulates the Wnt/β-catenin signalling pathway, ensuring controlled proliferation and differentiation of crypt stem cells. Loss or truncation of APC leads to accumulation of β-catenin in the nucleus, aberrant transcription of proliferative genes and the emergence of premalignant adenomas. Beyond its role in Wnt regulation, APC interacts with the cytoskeleton to influence cell migration, adhesion and chromosome segregation. Mutant APC also alters the tumour microenvironment, perturbing immune cell function and mitochondrial homeostasis, which together drive tumour initiation, heterogeneity and progression. Recent insights span structural conservation of APC domains, phenotypic diversity of APC-mutant tumours and the impact of APC deficiency on immune surveillance and mitochondrial quality control. These findings underscore the global significance of APC in CRC dynamics and inform strategies for early detection, risk stratification and targeted therapy.

Research from Nature Portfolio

Studies in a genetically engineered mouse model lacking the p53-inducible mitochondrial protein Mieap demonstrated that APC-driven tumourigenesis is exacerbated by defective mitochondrial quality control. Mieap deficiency in ApcMin/+ mice accelerated adenoma growth, increased reactive oxygen species and promoted malignant progression to adenocarcinoma, revealing that mitochondrial health is critical in suppressing APC-dependent intestinal tumours. This work highlights the interplay between APC mutation and organelle integrity as a key determinant of tumour dynamics.

Adenomatous Polyposis Coli Role in Colorectal Cancer Dynamics publication trend

The graph below shows the total number of articles in adenomatous polyposis coli role in colorectal cancer dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Wnt/β-catenin signalling: A pathway controlling gene transcription via β-catenin that regulates cell proliferation and differentiation in the intestine.

Tumour suppressor gene: A gene whose protein product restrains uncontrolled cell growth and whose loss or mutation promotes tumourigenesis.

Epithelial–mesenchymal transition (EMT): A cellular programme in which epithelial cells acquire migratory and invasive properties characteristic of mesenchymal cells.

Proteome: The complete set of proteins expressed in a cell, tissue or organism under specific conditions.

Phosphoproteome: The subset of the proteome comprising proteins modified by the addition of phosphate groups, often regulating activity.

Mitochondrial quality control: Cellular processes that maintain mitochondrial function and integrity through repair, removal or biogenesis.

Adenomatous polyposis: A condition marked by the development of numerous precancerous polyps in the colon, often due to APC mutations.

References

1. Mieap suppresses murine intestinal tumor via its mitochondrial quality control. Scientific Reports (2015).
2. Phenotypic Heterogeneity Analysis of APC-Mutant Colon Cancer by Proteomics and Phosphoproteomics Identifies RAI14 as a Key Prognostic Determinant in East Asians and Westerners. Molecular & Cellular Proteomics (2023).
3. The adenomatous polyposis coli protein 30 years on. Seminars in Cell and Developmental Biology (2023).
4. T cell migration and effector function differences in familial adenomatous polyposis patients with APC gene mutations. Frontiers in Immunology (2023).