Here we discovered that ABI1 inhibits EMT through suppressing FYN-STAT3 activation downstream from non-canonical WNT signaling thus providing a novel mechanism of prostate tumor suppression.
Immunohistochemistry studies showed increased levels of STAT3 and IL-6, but low levels of programmed cell death protein 4 (PDCD4), in prostate tumor epithelial cells compared to adjacent perinormal prostate epithelial cells.
Human prostate tumors with IL-6 elevation and loss of ESE3/EHF were associated with STAT3 activation and displayed upregulation of genes related to cell adhesion, cancer stem-like and metastatic spread.
To develop a potent strategy to increase therapeutic efficacy and reduce drug resistance in prostate cancer therapy, we combined two anti-cancer agents: T40214 (a p-Stat3 inhibitor) and JG244 (a HIF-1α inhibitor) together to treat nude mice bearing human prostate tumor (DU145) and immunocompetent mice (C57BL/6) bearing murine prostate tumor (TRAMP-C2).
The Fer tyrosine kinase cooperates with interleukin-6 to activate signal transducer and activator of transcription 3 and promote human prostate cancer cell growth.
Protein kinase Cepsilon interacts with signal transducers and activators of transcription 3 (Stat3), phosphorylates Stat3Ser727, and regulates its constitutive activation in prostate cancer.
Using immunohistochemical staining of tissue microarrays, we showed that these targets are enriched in breast and prostate tumors harboring activated STAT3.
Down-regulation of signal transducer and activator of transcription 3 expression using vector-based small interfering RNAs suppresses growth of human prostate tumor in vivo.
Using immunohistochemical staining of tissue microarrays, we showed that these targets are enriched in breast and prostate tumors harboring activated STAT3.
Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells.