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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\u2014particularly their pathological loss in digestive cancers\u2014remain poorly defined. Emerging evidence now reveals that cell type\u2010specific 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\/\u03b2\u2010catenin, and PDGFR\u03b1 signaling) to accelerate tumor initiation and progression. We further explore the therapeutic potential of pharmacologically restoring ciliary integrity to reverse pathway dysregulation, proposing cilia\u2010targeted strategies for early diagnosis and intervention in inflammation\u2010associated digestive malignancies.<\/jats:p>","DOI":"10.1002\/cbf.70102","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T11:29:34Z","timestamp":1752578974000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Primary Cilia: Hub of Cell Signal Transduction and Emerging Role in Digestive System Tumorigenesis"],"prefix":"10.1002","volume":"43","author":[{"given":"Wenyan","family":"Song","sequence":"first","affiliation":[{"name":"Beijing International Science and Technology Cooperation Base for Antiviral Drugs, Beijing Key Laboratory of Environmental and Viral Oncology, College of Chemistry and Life Science Beijing University of Technology Beijing 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