Future studies will identify novel Stat3 consensus sites that regulate HGF promoter activity and HGF expression preferentially in carcinoma cells and could lead to novel therapeutic drugs that specifically block HGF expression in mammary carcinoma cells, and which could be used in combined treatments to abrogate metastasis.
However, to date, the association of signal transducer and activator of transcription 3 (STAT3) with EMT, and its mediated tumor invasion and metastasis in HCC, remain elusive.
Mechanism investigation showed that the downregulation of Piwil3 significantly decreased the mRNA and protein expressions of metastasis-related genes, including RhoC, MTA1, MMP2 and MMP9, and also modulated the phosphorylation levels of JAK2 and STAT3 but not their protein levels.
Since STAT3 activation is involved in tumor progression and metastasis, we investigated the effect of GSNO in cell culture and mouse xenograft model of head and neck squamous cell carcinoma (HNSCC).
Our study indicates that NCAPG2 overexpression could drive HCC proliferation and metastasis through activation of the STAT3 and NF-κB/miR-188-3p pathways.
These results demonstrate that constitutively activated STAT3 regulates expression of MUC1, which mediates lung cancer cell survival and metastasis in vitro and in vivo.
STAT3, a cytoplasmatic latent transcription factor, is a hub protein for several oncogenic signalling pathways and up-regulates the expression of numerous genes involved in tumor cell proliferation, angiogenesis, metastasis and cell survival.
Quantitative genomic and functional analyses revealed that AKR1C1 directly interacted with STAT3 and facilitated its phosphorylation-thus reinforcing the binding of STAT3 to the promoter regions of target genes-and then transactivated these genes, which ultimately promoted tumor metastasis.
The discovery of a role for EIF3F-STAT3 interaction in the genetic control of cell migration and metastasis in human lung adenocarcinoma could lead to the development of diagnosis and therapeutic strategies.
We found that phosphorylation of STAT3 Y705 but not S727 promoted cancer cell EMT and metastasis through the Slug-mediated regulation of E-cadherin and Vimentin.
Simultaneously targeting PCa AR with siRNA and the CCL2/CCR2-STAT3 axis resulted in better suppression of PCa growth and metastasis in a xenograft PCa mouse model.
Signal transducer and activator of transcription 3 (STAT3), with abnormal expression and constitutive activation, has been reported to promote proliferation, metastasis, survival and angiogenesis of HCC cells.
CD5 antigen-like (CD5L), clusterin (CLUS) and C-C motif chemokine 14 (CCL14)], in transcription (e.g. protein SSX3 and signal transducer and activator of transcription 3 (STAT3)], in invasion and metastasis (e.g. alpha-2-HS-glycoprotein (FETUA)], in estrogen synthesis [aromatase (CYP19A1)] and other diverse biological roles [e.g. actin-related protein 2/3 complex subunit 4 (ARPC4), dual specificity mitogen-activated protein kinase kinase 4 (MP2K4), ectoderm-neural cortex protein 1 (ENC1), and matrix metalloproteinase-27 (MMP27)].