Gene Number: 324

Location: 5q22.2

Key Functions: Tumor suppression, Wnt signaling regulation, cell cycle control, genomic stability

The APC (adenomatous polyposis coli) gene encodes a large tumor suppressor protein that acts as a cornerstone in maintaining epithelial tissue integrity and controlling cellular proliferation. APC is best known for its central role in the Wnt/β-catenin signaling pathway, a system crucial for regulating cell fate, division, and differentiation.

Under normal conditions, APC forms a complex with AXIN, GSK-3β, and CK1, which together promote the phosphorylation and subsequent degradation of β-catenin. This process prevents β-catenin from accumulating in the cytoplasm and entering the nucleus, where it could otherwise activate genes that drive uncontrolled cell growth. When APC is lost or mutated, β-catenin escapes this regulation, leading to continuous activation of proliferative genes and, consequently, tumor formation.

Beyond Wnt/β-catenin signaling, APC contributes to chromosomal stability by interacting with the cytoskeleton and regulating microtubule attachment during mitosis. Defects in this function can result in aneuploidy and genomic instability—key hallmarks of cancer progression.

Genetically, loss-of-function mutations in APC are the initiating event in familial adenomatous polyposis (FAP), an inherited condition characterized by hundreds to thousands of precancerous polyps in the colon. Somatic mutations in APC are also among the earliest and most common events in sporadic colorectal carcinogenesis, often representing the first step in the classical adenoma-to-carcinoma sequence.

In essence, APC functions as the genomic gatekeeper of the intestinal epithelium—its inactivation removes a vital safeguard against uncontrolled proliferation, setting the stage for malignant transformation.