What is STAT3 in cancer?
Cancer cell-intrinsic signal transducer and activator of transcription 3 (STAT3) activity supports many of the hallmarks of cancer, including cell growth, proliferation, survival, immune evasion, metastasis and angiogenesis.
Why is STAT3 important?
STAT3 signalling is a major intrinsic pathway for cancer inflammation because it is frequently activated in malignant cells and capable of inducing a large number of genes that are crucial for inflammation (TABLE 2).
What is STAT3 signalling?
Introduction. Signal transducer and activator of transcription 3 (STAT3) is a member of a family of seven proteins (STATs 1, 2, 3, 4, 5a, 5b, and 6) that relay signals from activated cytokine and growth factor receptors in the plasma membrane to the nucleus, where they regulate gene transcription (1–3).
What is the STAT3 pathway?
STAT3 signaling is a major intrinsic pathway for cancer inflammation because it is often activated in tumor-associated immune and inflammatory cells as well as malignant cells and is capable of inducing a large number of genes that are crucial for inflammation including IL-6, 10, 11, 17, 23, CXCL12, and COX-2 .
How do you inhibit STAT3?
Specific STAT3 direct inhibitors consist of SH2 ligands, including G quartet oligodeoxynucleotides (ODN) and small molecules, they induce cell death in tumor cells in which STAT3 is activated. STAT3 can also be inhibited by decoy ODNs (dODN), which bind STAT3 and induce cell death.
How is STAT3 activated?
STAT3 is activated by several pro-inflammatory cytokines, including interleukin-6 (IL-6)24,25,26, which is a prime target for therapeutic intervention in several inflammatory diseases including rheumatoid arthritis, Still’s disease and giant cell arthritis.
What is STAT3 gene?
STAT3 GOF disease is caused by gain- of-function mutations in the STAT3 gene. This gene provides instructions for production of the STAT3 protein, part of the STAT family of proteins. Various mutations have been identified across the length of the STAT3 protein. STAT proteins play an essential role.
Where is STAT3 found?
STAT3 is found in the cytoplasm and is activated in response to stimuli from the cytokines. Activated STAT3 regulates the transcription of genes controlling cell survival and proliferation and regulates the expression of antiapoptotic and immune response genes [128–130].
What does STAT3 protein do?
Through its regulation of gene activity, the STAT3 protein is involved in many cellular functions. It helps control cell growth and division (proliferation), cell movement (migration), and the self-destruction of cells (apoptosis).
What induces STAT3?
SOCS3, the major negative regulator of STAT3, is induced by tyrosine-phosphorylated STAT3 and terminates STAT3 phosphorylation about 2 h after initial exposure of cells to members of the IL-6 family of cytokines by binding cooperatively to the common receptor subunit gp130 and JAKs 1 and 2.