The Significance of STAT3 in Colonic Diseases: A Comprehensive Study of Pathological Roles and Therapeutic Implications

The transcriptional regulator signal transducer and activator of transcription 3 (STAT3) plays pivotal roles in vertebrate development and the functionality of mature tissues, particularly in modulating inflammation and immune responses. Mutations in STAT3 in humans are associated with various diseases, including immunodeficiencies, autoimmune disorders, and multiple cancers. Notably, both aberrant hyperactivation and inactivation of STAT3 are linked to disease manifestations, underscoring the need for tightly regulated STAT3 activity to maintain health. In inflammatory bowel disease (IBD), STAT3 exhibits abnormal activation in colonic tissues, primarily driven by a range of pro-inflammatory cytokines. This dysregulation compromises the integrity of the intestinal mucosal barrier and leads to an exaggerated innate immune response and heightened Th17 cell activity. Moreover, persistent STAT3 activation is implicated in the pathogenesis of colorectal cancer (CRC), highlighting its critical regulatory role in inflammation associated with cancer-induced colitis. Elevated STAT3 expression is frequently observed in CRC cases. This study delves into STAT3’s multifaceted roles in various cellular processes, including proliferation, migration, differentiation, motility, and the inflammatory response, specifically focusing on their implications in colitis and colorectal cancer. We further explore therapeutic strategies to modulate STAT3 signaling pathways, which could provide innovative approaches for managing STAT3-dependent colonic disorders.