STAT3beta, a distinct isoform from STAT3

STAT3β is an isoform of STAT3 (signal transducer and activator of transcription 3) that differs from the STAT3α isoform by the replacement of the C-terminal 55 amino acid residues with 7 specific residues. The constitutive activation of STAT3α plays a pivotal role in the activation of oncogenic pathways, such as cell proliferation, maturation and survival, while STAT3β is often referred to as a dominant-negative regulator of cancer. STAT3β reveals a "spongy cushion" effect through its cooperation with STAT3α or forms a ternary complex with other co-activators. Especially in tumour cells, relatively high levels of STAT3β lead to some favourable changes. However, there are still many mechanisms that have not been clearly explained in contrast to STAT3α, such as STAT3β nuclear retention, more stable heterodimers and the prolonged Y705 phosphorylation. In addition to its transcriptional activities, STAT3β may also function in the cytosol with respect to the mitochondria, cytoskeleton rearrangements and metastasis of cancer cells. In this review, we summarize the mechanisms that underlie the unique roles of STAT3β combined with total STAT3 to enlighten and draw the attention of researchers studying STAT3 and discuss some interesting questions that warrant answers.