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STAT 3 the oncogene – still eluding therapy?
Author(s) -
Wake Matthew S.,
Watson Christine J.
Publication year - 2015
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13285
Subject(s) - stat , stat4 , jak stat signaling pathway , cancer research , stat protein , biology , transcription factor , stat6 , gene silencing , carcinogenesis , cytokine , microbiology and biotechnology , stat3 , signal transduction , immunology , cancer , gene , receptor tyrosine kinase , interleukin 4 , genetics
The STAT family of transcription factors (signal transducers and activators of transcription) transduce signals from cytokine receptors to the nucleus, where STAT dimers bind to DNA and regulate transcription. STAT 3 is the most ubiquitous of the STAT s, being activated by a wide variety of cytokines and growth factors. STAT 3 has many roles in physiological processes such as inflammatory signalling, aerobic glycolysis and immune suppression, and was also the first family member shown to be aberrantly activated in a wide range of both solid and liquid tumours. STAT 3 promotes tumorigenesis by regulating the expression of various target genes, including cell‐cycle regulators, angiogenic factors and anti‐apoptosis genes. Paradoxically, in some circumstances, STAT 3 signalling induces cell death. The best known example is the involuting mammary gland, where STAT 3 is essential for induction of a lysosomal pathway of cell death. Nevertheless, direct silencing or inhibition of STAT 3 diminishes tumour growth and survival in both animal and human studies. This suggests that abolishing STAT 3 activity may be an effective cancer therapeutic strategy. However, despite this potential as a therapeutic target, and the extensive attempts by many laboratories and pharmaceutical companies to develop an effective STAT 3 inhibitor for use in the clinic, no direct STAT 3 inhibitor has been approved for clinical use. In this review, we focus on the role of STAT 3 in tumorigenesis, and discuss its potential as a therapeutic target for cancer treatment.