Regulation of EMT by STAT3 in gastrointestinal cancer (Review)

Gastrointestinal (GI) cancer is characterized by its aggressiveness and tendency to metastasize at early stage. Epithelial-mesenchymal transition (EMT), commonly known as the preparing step of metastasis, may account for the aggressive phenotype of GI cancer cells. The process of EMT is finely orchestrated by multiple layers of regulators. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor constitutively activated in diverse malignancies. Recent studies have suggested an involvement of STAT3 in GI cancer EMT. In this review, we first take an insight into the oncogenic functions of STAT3 in GI cancer, and then summarize the possible mechanisms by which STAT3 regulates the EMT process. Through the extensive interactions with EMT-inducing transcription factors and non-coding RNAs, and crosstalk with other signaling pathways, STAT3 has been demonstrated to promote the mesenchymal and invasive phenotype of GI cancer, which provides rationales for specifically targeting STAT3 to prevent and reverse the progression of GI cancer.