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Significance The transcription factor STAT3 plays pivotal roles in various physiological processes, including differentiation of Th cells. Its deregulation results in serious diseases, including inflammatory diseases and cancer. Understanding how STAT3 activity is regulated is important for deciphering the pathogenesis of such diseases. In this study, we identified a protein called FAM64A, which promotes STAT3 activity through modulating the DNA-binding activity of STAT3. Consequently, FAM64A also promotes Th17 differentiation and development of colitis and colitis-associated cancer. This study reveals a previously unreported function of FAM64A in the regulation of inflammation and tumorigenesis and provides a potential therapeutic target for inflammatory diseases and cancer.

FAM64A positively regulates STAT3 activity to promote Th17 differentiation and colitis-associated carcinogenesis