Primary Cilia: Hub of Cell Signal Transduction and Emerging Role in Digestive System Tumorigenesis

Abstract

Primary cilia, microtubule-based sensory organelles that protrude from the cell surface, are integral to sensing the cellular microenvironment and mediating intercellular signal transduction. They play a crucial role in maintaining homeostasis of major human organs. While primary cilia have been extensively characterized in other organs and linked to tumorigenesis, their specific roles within the digestive system—particularly their pathological loss in digestive cancers—remain poorly defined. Emerging evidence now reveals that cell type-specific ciliary loss (e.g., in cholangiocytes, pancreatic ductal epithelial cells, and gastrointestinal stromal cells and fibroblasts) disrupts critical signaling homeostasis, driving malignant transformation in disorders such as cholangiocarcinoma, chronic pancreatitis, pancreatic ductal adenocarcinoma, and colon cancer. This review synthesizes how ciliary dysfunction in digestive cell subtypes alters key oncogenic pathways (e.g., Hedgehog, Wnt/β-catenin, and PDGFRα signaling) to accelerate tumor initiation and progression. We further explore the therapeutic potential of pharmacologically restoring ciliary integrity to reverse pathway dysregulation, proposing cilia-targeted strategies for early diagnosis and intervention in inflammation-associated digestive malignancies.