S3I-201 (NSC 74859) is a chemical probe inhibitor of Stat3 activity, which was identified from the National Cancer Institute chemical libraries by using structure-based virtual screening with a computer model of the Stat3 SH2 domain bound to its Stat3 phosphotyrosine peptide derived from the x-ray crystal structure of the Stat3beta homodimer. S3I-201 inhibits Stat3.Stat3 complex formation and S...

Stat3 plays diverse roles in biological processes including cell proliferation, survival, apoptosis, and inflammation. Very little is known regarding its activation and function in the lung during acute inflammation. We now show that Stat3 activation was triggered in lungs and in alveolar macrophages after intrapulmonary deposition of IgG immune complexes in rats. Low levels of constitutive Sta...

Hyperphosphorylation at the Y705 residue of signal transducer and activator of transcription 3 (STAT3) is implicated in tumorigenesis of leukemia and some solid tumors. However, its role in the development of colorectal cancer is not well defined. To rigorously test the impact of this phosphorylation on colorectal tumorigenesis, we engineered a STAT3 Y705F knock-in to interrupt STAT3 activity i...

Interleukin-6 (IL-6) initiates STAT3 signaling in plasma membrane rafts with the subsequent transit of Tyr-phosphorylated STAT3 (PY-STAT3) through the cytoplasmic compartment to the nucleus in association with accessory proteins. We initially identified caveolin-1 (cav-1) as a candidate STAT3-associated accessory protein due to its co-localization with STAT3 and PY-STAT3 in flotation raft fract...

In the liver, signal transducer and activator of transcription 3 (STAT3) plays an important role in the suppression of gluconeogenic enzyme expression. While obesity-associated endoplasmic reticulum (ER) stress has been shown to increase hepatic gluconeogenic enzyme expression, the role of ER stress in STAT3-dependent regulation of such expression is unclear. The current study aimed to elucidat...

Background The serendipitous discovery of heavy-chain antibodies devoid of light chains in camelids and the subsequent development of VHHs (variable region of camelid heavy chain) have provided a very important tool for research and possibly for therapeutics. In this study, we synthesized single-domain 15-kDa antibody SBT-100 (anti-STAT3 B VHH13) against human STAT3 (signal transducer and activ...

Signal transducer and activator of transcription 3 (STAT3) protein has been documented as a significant mediator of interferon (IFN) signaling. Physiological STAT3 phosphorylation involves tyrosine (Y705) and serine (S727) activation. Impairment of STAT3 protein levels and/or of STAT3 phosphorylation after IFN treatment has been found in many pathological conditions such as cancer, immunopathy ...

Wnt signalling and the signal transducer and activator of transcription 3 (STAT3) are oncogenic signalling pathways which are deregulated in colorectal cancer (CRC). Here we investigated the interaction of these two pathways. Firstly, we investigated biochemical interaction by inhibiting STAT3 and β-catenin (through gene knock-down and dominant-negative TCF4 expression) in nine CRC cell lines. ...

Stat3 activation has been associated with cytokine-induced proliferation, anti-apoptosis, and transformation. Constitutively activated Stat3 has been found in many human tumors as well as v-abl- and v-src-transformed cell lines. Because of these correlations, we examined directly the relationship of activated Stat3 to cellular transformation and found that wild-type Stat3 enhances the transform...

Abstract p27 normally inhibits cell cycle progression and growth. In cancers, deregulated acts as an oncogene to promote metastasis when phosphorylated by PI3K-activated kinases at T157 T198 (p27pTpT). We showed p27pTpT transcriptionally co-activates cJun induces STAT3 activation. Here, we pursue the hypothesis that target genes expand cancer stem cells (CSC) inflammation. triple negative breas...