Proteomic and genomic analyses identified an iron-regulated signaling axis mediated by cyclin-dependent kinase 1 (CDK1), JAK1, and STAT3 in CRC progression.
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.
Thus, our study indicates that the high level of IL-35 in colorectal cancer promotes the production of IL-35 via STAT1 and STAT3, which suppresses T cell proliferation and may participate in tumor immunotolerance.
Taken together, our results indicated that nifuroxazide could effectively inhibit tumor metastasis by mediating Stat3 pathway and it might have a therapeutic potential for the treatment of CRC.
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.
In conclusion, microRNA-375 might function as a tumor-repressive gene to inhibit cell proliferation, mainly through targeting both JAK2/STAT3 and MAP3K8/ERK signaling pathways in colorectal cancer.
Antagonistic Effects of p53 and HIF1A on microRNA-34a Regulation of PPP1R11 and STAT3 and Hypoxia-induced Epithelial to Mesenchymal Transition in Colorectal Cancer Cells.
Scorpion Venom Causes Upregulation of p53 and Downregulation of Bcl-x<sub>L</sub> and BID Protein Expression by Modulating Signaling Proteins Erk<sup>1/2</sup> and STAT3, and DNA Damage in Breast and Colorectal Cancer Cell Lines.
Finally, enhancer 1 acquired the binding of STAT3 in stage I CRC, and inhibition of STAT3 phosphorylation restored PTX3 activity and decreased enhancer 1 methylation.
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.
Downregulation of RNF6 impaired the colorectal cancer cell proliferation and invasion <i>in vitro</i> and <i>in vivo</i> RNF6 may activate the JAK/STAT3 pathway and increase pSTAT3 levels by inducing the ubiquitination and degradation of SHP-1.<b>Conclusions:</b> Genomic amplification drives RNF6 overexpression in colorectal cancer.
We found that using interleukin 6 to induce p-STAT3 activation in colorectal cancer cell lines can result in vasculogenic mimicry and using AG490 to suppress p-STAT3 activation restrained vasculogenic mimicry.
The development of colorectal cancer (CRC) is strongly associated with the imbalance of various intracellular signal transduction cascades, including protein kinase B (AKT), mitogen-activated protein kinase 1 (MAPK), signal transducer and activator of transcription 3 (STAT3), as well as crosstalk between these signaling networks.
Although there was no difference in overall survival between groups in the overall unselected population, STAT3 might be an important target for the treatment of colorectal cancer with elevated pSTAT3 expression.
The result obtained from quantitative western blot analysis demonstrated that the CRC condition was produced by the IL-6 induced activation/phosphorylation of JAK2 and STAT3 and further down-regulated with M1 treatment.
Further functional experiments indicated that GACAT3 could directly upregulate SP1 and STAT3 expressions by functioning as a competing endogenous RNA for miR-149, and consequentially, promoting CRC cell proliferation and invasion in vitro.
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.
Furthermore, the STAT3-S1PR pathway that has been reported previously to mediate the effect of SphK1 on colorectal cancers was not altered by SphK1 deletion in liver cancer.