Blockade of STAT3 activation in CRC-derived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth.
Overall data suggests that CRC population was STAT3/pSTAT3 immunoreactive in a stage specific manner and STAT3 protects cancerous colorectal epithelial cells from apoptosis.
We approached mechanisms leading to STAT3 activation in CRC by mimicking "tumor-like" growth conditions and forcing cell-cell contacts of HT-29 CRC cells in culture.
This finding supports the notion that the combination of inappropriate STAT3 and AP-1 activities drives elevated MMP-1 expression and tissue invasion in colorectal cancer and is of clinical relevance.
Moreover, in therapeutic proof-of-concept studies, these nanoparticles were effective in silencing the expression of two proteins that are key to cancer growth and metastasis (signal transducer and activator of transcription 3 and focal adhesion kinase) in orthotopic mouse models of ovarian and colorectal cancer.
To investigate the role of both JAK2 and STAT3 in the mechanism underlying CRC apoptosis, we inhibited JAK2 with AG490 and depleted STAT3 with a small interfering RNA.
We hypothesized that ganetespib, a potent HSP90 inhibitor, would disrupt angiogenesis in colorectal cancer (CRC) through inhibition of HIF-1α and STAT-3.
The development of colorectal cancer (CRC) is strongly correlated with the aberrant activation of multiple intracellular signaling transduction cascades including STAT3, ERK, JNK and p38 pathways which usually function redundantly.
We have recently reported that STAT3 gene expression correlates with resistance of CRC cell lines to 5-fluorouracil (5-FU)-based chemoradiotherapy (CT/RT).
These data suggest that miR-124 serves as a tumor suppressor by targeting STAT3, and call for the use of miR-124 as a potential therapeutic tool for CRC, where STAT3 is often hyper-activated.
Tumor angiogenesis is highly regulated by multiple intracellular signaling transduction cascades such as Hedgehog, STAT3, Akt and p70S6K pathways that are known to malfunction in many types of cancer including colorectal cancer (CRC).
Our data revealed that i) in CRC cells, STAT3 was continuously activated by phosphorylation, and SOCS3 was at a relative low expression level; and ii) AdCN305-cppSOCS3 inhibited the continuous activation of the JAK/STAT3 pathway, suppressed CRC cell growth and induced apoptosis, in vitro and in vivo.
The present review details the mechanisms and roles of the IL-6/JAK/STAT3 pathway in CRC, describes current therapeutic strategies, and the search for potential therapeutic approaches to treat CRC.
Here, we determined that exposure of human colorectal cancer (CRC) cells to the cytokine IL-6 activates the oncogenic STAT3 transcription factor, which directly represses the MIR34A gene via a conserved STAT3-binding site in the first intron.