DUSP6 expression

Mechanistically, DUSP6 dephosphorylates phospho-Y2116, which in turn reduces NTM ubiquitination, leading to increased NTM stability and transcriptional activity. As a result, the expression of Notch1-targeted proliferation genes is increased to promote tumour cell growth.

Resistance developed in DUSP6 KO cells, indicating a bypass mechanism. Although targeting ASCL1 remains a challenge, our findings suggest that expression of ASCL1, DUSP6 and low phospho-ERK1/2 identify neuroendocrine lung cancers for which DUSP6 may be a therapeutic target.

Moreover, docking experiments have indicated that DUSP6 expression is enhanced when bound by Calcium saccharate, which also inhibits RCC cell proliferation, metabolic rewiring, and sunitinib resistance. In conclusion, our study identifies Calcium saccharate as a prospective pharmacological therapeutic approach for RCC.

Collectively, these findings suggest that SCO inhibited the expression of PD-L1 in breast cancer cells by upregulating MKP-3 expression. Therefore, SCO may serve as an innovative combinatorial agent for cancer immunotherapy.

Naporafenib, with or without spartalizumab, showed an acceptable safety profile, pharmacodynamic activity and limited antitumor activity. Additional naporafenib combination therapies are currently under investigation.

This promotes accumulation of mitochondrial reactive oxygen species and, thereby, DNA damage and apoptotic cell death in CLL cells. Finally, we observe that DUSP1/6 inhibition is particularly effective against treatment-resistant CLL and therefore suggest transient DUSP1/6 inhibition as a promising treatment concept to eliminate drug-resistant CLL cells.

In addition, DUSP6 expression substantially decreased in fibrotic kidneys, and it might be involved in MCM6-induced renal fibrosis by regulating the activation of ERK/GSK-3β/Snail1 signaling. In conclusion, our results highlight the significance of MCM6 in renal fibrosis, providing a potential therapeutic target for patients with chronic kidney disease.

Compared with paclitaxel, the tumor inhibition effect of the two drugs was similar. However, angelicin did not cause weight loss and had lower toxicity. In sum, Angelicin has antitumor effects on OSCC in vitro and vivo by negatively regulating the DUSP6 mediated c-MYC signaling pathway.

This finding demonstrated that BOP1 promoted CaP progression by regulating the DUSP6/MAPK pathway.

Restoration of DUSP6 rescues the effects generated by miR-BART11-3p in GC cells, and blocking ERK phosphorylation with Trametinib augments JNK and p38 phosphorylation and inhibits the effects of miR-BART11-3p-expressing AGS cells, suggesting that miR-BART11-3p promotes cell proliferation, migration, and invasion by modulating DUSP6-MAPK axis in EBVaGC. The findings presented in this study provide new mechanisms into the tumorigenesis in EBVaGC and new avenues for the development of therapeutic strategies to combat EBVaGC targeting miR-BART11-3p or phospho-ERK.

TGFβ1 induced EMT which was accompanied by increased activity of MAPKs, and led to marked changes in expressions of several DUSPs in SKOV3 cells.

The 5-gene panel successfully stratifies low- and high-risk patients, and may be a promising tool for predicting outcomes in early-stage NSCLC patients.; Cell and molecular biology; General respiratory patient care