The T-box factors belong to an ancient protein family, which comprises a cluster of evolutionarily-conserved transcription factors that regulate gene expression and that are crucial to embryonic development. T-box transcription factor 3 (Tbx3) is a member of this family, is expressed in some tissues, and is a key regulator in many critical organs, including the heart, mammary gland, and limbs. Overexpression of Tbx3 is associated with a number of cancers, including head and neck squamous cell carcinoma, gastric, breast, ovary, cervical, pancreatic, bladder and liver cancers, as well as melanoma. Tbx3 promotes tumor development by modulating cell proliferation, tumor formation, metastasis, cell survival and drug resistance. Moreover, there is strong evidence that Tbx3 regulates stem cell maintenance by controlling stem cell self-renewal and differentiation. Verification of the upstream regulatory factors and potential molecular mechanism of Tbx3, being able to explain the function of Tbx3 in carcinogenic effects and stem cell maintenance, will make a valuable contribution to stem cell and cancer research. This review provides an insight into the current research on Tbx3 and explores the significance of Tbx3 in stem cells and tumorigenesis.
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