What genes are regulated by STAT3?

Given its ability to regulate both oncogenes and tumor suppressor genes, STAT3 has been reported to promote and inhibit oncogenesis. STAT3 has been shown to induce cancers of the breast [21,22], prostate [11] and skin [23,24].

Why STAT3 is a unique target for cancer therapy?

Besides its canonical function as transcription factor, STAT3 plays a distinct role in the mitochondria, where it supports Ras-dependent malignant transformation [107], promotes autophagy, and restrains ROS levels, thus increasing cancer cell survival [108].

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.

What is STAT3 mutation?

STAT3 loss- of-function mutations are responsible for hyper- immunoglobulin E syndrome, also called Job’s syndrome, which is characterized by recurrent skin infections, unusual eczema-like skin rashes, and susceptibility to severe lung infections.

How does STAT3 promote resistance to therapy?

Persistent STAT3 activity can also enhance stem cell-like and mesenchymal properties, making obstruction of the pathway through which it signals a potentially attractive therapeutic strategy. In several studies, increasing in number through the last few years, STAT3 has also been implicated in resistance to radiation.

What is a STAT3 inhibitor?

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.

What is the function of STAT3?

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). The STAT3 protein is active in tissues throughout the body.

What does the STAT3 gene do?

What is the function of the STAT3 gene?

The protein encoded by the STAT3 gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators.

Are there any small molecule inhibitors of STAT3?

Moreover, STAT3 inhibitors, such as the small-molecule inhibitor BBI-608 and monoclonal antibody SBT-100 have obtained orphan drug identification in pancreatic cancer and are undergoing clinical phase ΙΙΙ and Ι study, respectively. The targeted inhibition of STAT3 represents a promising therapeutic strategy for pancreatic cancer.

How is STAT3 activated in the JAKs pathway?

The IL-6/IL-6R/gp130 complex activates the JAKs by phosphorylation which results in STAT3 phosphorylation and activation. STAT3 activation can be achieved by phosphorylation via other factors such as growth factors (i.e. FGF, IGF and EGF). These growth factors bind to their cognate membrane receptors.

What is the role of STAT3 in pancreatic cancer?

The key role of STAT3 in promoting pancreatic cancer progression has been proven, but effective interventions that suppress STAT3 activities are limited. The development of novel anticancer agents that directly target STAT3 may have potential clinical benefits for pancreatic cancer treatment.