In addition, suppression of ZIC5 or PDGFD expression decreased levels of phosphorylated focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) which are associated with PCa and CRC aggressiveness.
Herein, we demonstrate that the active form of Rac family small GTPase 1 (RAC1-GTP) is overexpressed in CRCs and promotes the EMT-mediated invasion of CRC cells through activation of the signal transducers and activators of transcription 3 (STAT3) pathway.
In conclusion, Talin1 knockdown may prevent the proliferation and migration of CRC cells by downregulating various factors involved in the epithelial-to-mesenchymal transition process, such as phosphorylated STAT3 and vimentin; therefore, talin1 may provide a novel therapeutic target for CRC.
We have recently reported that STAT3 gene expression correlates with resistance of CRC cell lines to 5-fluorouracil (5-FU)-based chemoradiotherapy (CT/RT).
This interactions leads to the de-repression of genes downstream of STAT3 and consequentially inhibition of CRC cell proliferation and tumor growth in vitro and in vivo by extending the G0/G1-S phase transition.
More importantly, the specific STAT3 inhibitor S3I-201 and IL-6R inhibitor tocilizumab abolished the discrepancy of growth and metastasis capacity between lnc-DILC-interference CRC cells and control cells, which further confirmed that IL-6/STAT3 signaling was required in lnc-DILC-disrupted CRC cell growth and metastasis.
Our findings provide insight into the important role of SIRT2 in colon tumour angiogenesis and suggest that SIRT2/STAT3/VEGFA might be a novel prognostic biomarker and a potential therapeutic target for patients with colorectal cancer.
The present study examines the relationship between tumor total STAT3 and phosphorylated STAT3<sub>Tyr705</sub> (pSTAT3) expression, host inflammatory responses, and survival in patients undergoing resection of stage I-III colorectal cancer.<b>Experimental Design:</b> Immunohistochemical assessment of STAT3/pSTAT3 expression was performed using a tissue microarray and tumor cell expression divided into tertiles using the weighted histoscore.
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.
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.
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 searched the available articles reporting the prognostic value of p-STAT3 in patients with cancers of the digestive system, mainly including colorectal cancer, gastric cancer, hepatocellular carcinoma, esophagus cancer and pancreatic cancer.
Taken together, our findings suggest BOL is a novel therapeutic STAT3 inhibitor that can be used either alone or in combination with MEK inhibitors for the treatment of human CRC.
Our findings indicate that c-MET/STAT3-dependent upregulation of c-FLIPL expression is an important escape mechanism following MEKi treatment in BRAFMT colorectal cancer.
We found that APC loss also results in up-regulation of IL-6 signal transducer (IL-6ST/gp130), thereby activating Src family kinases (SFKs), YAP, and STAT3, which are simultaneously up-regulated in the majority of human CRC.
Together, this study proposes the existence of an aberrant IL-6/STAT3/Fra-1 signaling axis leading to CRC aggressiveness through EMT induction, which suggests novel therapeutic opportunities for the malignant disease.
Overall data suggests that CRC population was STAT3/pSTAT3 immunoreactive in a stage specific manner and STAT3 protects cancerous colorectal epithelial cells from apoptosis.
Using a unique systems biology approach, we identified JAK1/2-dependent activation of STAT3 as the key mediator of resistance to MEK inhibitors in KRASMT CRC in vitro and in vivo.