ERp57 is an endoplasmic reticulum (ER) resident thiol disulfide oxidoreductase. Using the gene trap technique, we created a ERp57-deficient mouse model. Targeted deletion of the Pdia3 gene, which encodes ERp57, in mice is embryonic lethal at embryonic day (E) 13.5. Beta-galactosidase reporter gene analysis revealed that ERp57 is expressed early on during blastocyst formation with the highest ex...

Metastasis and disease relapse are hypothesized to result from tumor initiating cells (TICs). Previously, we have defined a CD44+/CD24-/low mammosphere-forming tumorigenic 493-gene signature in breast cancer. Stat3 was identified as a critical node in self-renewal based on an ongoing lentiviral shRNA screen being conducted in two breast cancer cell lines SUM159 and BT549. In corroborating work,...

Mutations in the gene coding for the integral membrane protein polycystin-1 (PC1) are the cause of most cases of autosomal-dominant polycystic kidney disease (ADPKD), a very common disease that leads to kidney failure and currently lacks approved treatment. Recent work has revealed that PC1 can regulate the transcription factor STAT3, and that STAT3 is aberrantly activated in the kidneys of ADP...

STAT3 is both a transcription activator and an oncogene that is tightly regulated under normal physiological conditions. However, abundant evidence indicates that STAT3 is persistently activated in several cancers, with a crucial position in tumor onset and progression. In addition to its traditional role in cancer cell proliferation, invasion, and migration, STAT3 also promotes cancer through ...

Tyrosine phosphorylation is a hallmark for activation of STAT proteins, but their transcriptional activity also depends on other secondary modifications. Type I IFNs can activate both the ISGF3 (STAT1:STAT2:IRF9) complex and STAT3, but with cell-specific, selective triggering of only the ISGF3 transcriptional program. Following a genome-wide RNAi screen, we identified the SIN3 transcription reg...

Dendritic cells (DCs) must achieve a critical balance between activation and tolerance, a process influenced by cytokines and growth factors. IL-10, which transduces signals through Stat3, has emerged as one important negative regulator of DC activation. To directly examine the role Stat3 plays in regulating DC activity, the Stat3 gene was targeted for deletion with a CD11c-cre transgene. Stat3...

Type I IFNs are crucial cytokines of innate immunity for combating viral infections. Signaling through type I IFN receptors triggers the activation of STAT proteins, including STAT1, STAT2, and STAT3. Although an essential role of STAT1 and STAT2 for type I IFN-induced antiviral response has been well established by studies of gene-targeted mice and human mutations, the role of STAT3 for this r...

BACKGROUND Diffuse infiltration remains the fulcrum of glioblastoma's incurability, leading inevitably to recurrence. Therefore, uncovering the pathological mechanism is imperative. Because signal transducer and activator of transcription 3 (STAT3) correlates with glioma malignancy and predicts poor clinical outcome, we determined its role in glioma single cell infiltration and tumor growth. ...

BACKGROUND/AIM Gender-associated dimorphism in renal oxidative stress may be related to the protective effects of estrogens or the adverse effects of testosterone. Signal transducer and activator of transcription-3 (STAT3)-dependent transcription is vital in renal antioxidant responses, which may be differentially regulated by sex hormones. MATERIALS AND METHODS Renal proximal tubule cells we...

Angiogenesis is the development of new blood vessels, which is required for tumor growth and metastasis. Signal transducer and activator of transcription factor 3 (STAT3) is a transcription factor that regulates a variety of cellular events including proliferation, differentiation and apoptosis. Previous studies revealed that activation of STAT3 promotes tumor angiogenesis. In this review, we d...