The combination of proteomic and transcriptomic analysis as well as functional assays revealed several new KLK14 substrates (agrin, desmoglein 2, vitronectin, laminins) and KLK14-regulated genes (Interleukin 32, midkine, SRY-Box 9), particularly an involvement of the mitogen-activated protein kinase 1 and interleukin 1 receptor pathways, and an involvement of KLK14 in the regulation of cellular migration, supporting its involvement in aggressive features of PCa progression.
Knockdown of COPS3 inhibited the progress of PCa through reducing the levels of phosphorylated P38 MAPK and impaired the epithelial-mesenchymal transition process.
Our findings indicate that loss of function of DUSP22 in PCa cells leads to aberrant activation of both EGFR-ERKs and AR signaling and ultimately progression of PCa, supporting the potential for novel therapeutic design of harnessing DUSP22 in the treatment of PCa.-Lin, H.-P., Ho, H.-M., Chang, C.-W., Yeh, S.-D., Su, Y.-W., Tan, T.-H., Lin, W.-J.
We have found that the nuclear ERK-selective phosphatase DUSP5 is downregulated in colorectal tumours and cell lines, as previously observed in gastric and prostate cancer.
Rescue experiments also demonstrated that restored MAPK1 expression reversed the tumor-suppressing effects of miR-212 on PCa cell proliferation, invasion, and apoptosis.
The chrysin-mediated intracellular signaling pathways suppressed phosphoinositide 3-kinase (PI3K) and the abundance of AKT, P70S6K, S6, and P90RSK proteins, but stimulated mitogen-activated protein kinases (MAPK) and activation of ERK1/2 and P38 proteins in the prostate cancer cells.
With inhibition of p38, ERK, and JNK, the TSP-2-induced cell migration and MMP-2 expression were abolished, indicating that the TSP-2's effect on PCa is MAPK dependent.
<b>Conclusion:</b> These data suggest that exenatide and liraglutide attenuate prostate cancer growth through regulating P38 pathway by binding with GLP-1R.
In conclusion, our findings have identified critical molecular mechanisms involving ERK-mediated ERG activation that could be exploited for therapeutic intervention in ERG-positive prostate cancers.
Together, we have identified an association of genetic variants and genes in the RTK/ERK pathway with prostate cancer aggressiveness, and highlighted the potential importance of CCND2 in prostate cancer susceptibility and tumor progression to metastasis.
Function of E2F5 and p38 in prostate cancer was investigated using siRNA-treatment of PC3 cell-line followed by analyses of associated components and cell cycle.
Finally, the results demonstrated that AQP3 upregulated matrix metalloproteinase‑3 (MMP‑3) expression and secretion in prostate cancer cells via activation of the ERK pathway.