While phosphatases up-regulated in cancer counteract the JAK-mediated phosphorylation or terminate the activation of STAT3 [70,71,75], PIAS proteins which are upregulated in breast cancer, inhibit STAT3 DNA binding activity [73,76], and SOCS proteins, that inhibit JAK-STAT3 signalling through negative feedback, are downregulated in breast cancer [77]. This evidence concerns the gene CISH and breast cancer.