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Transcription factor 21 (TCF21) is a basic helix–loop–helix transcription factor that binds to DNA and regulates cell differentiation and cell fate specification through mesenchymal–epithelial transition during development. The TCF21 gene is epigenetically inactivated in many types of human cancers and exerts a wide variety of functions, including the regulation of epithelial–mesenchymal transition, invasion, metastasis, cell cycle, and autophagy. This review focuses on research progress in relation to the roles of TCF21 in tumor development. We systematically consider multiple pathological functions of TCF21 in various cancers, revealing the molecular bases of its diverse biological roles and providing new directions for future research.

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