ERK is a negative feedback regulator for IFN-γ/STAT1 signaling by promoting STAT1 ubiquitination

Zhang, Ying; Chen, Yelong; Liu, Zhaoyong; Lai, Raymond

doi:10.1186/s12885-018-4539-7

Cited by 29 publications

(23 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…24,25 Persistent activation of ERK can promote the degradation of STAT1, a signal transduction and transcription activating factor, thus promoting cell proliferation and inhibiting apoptosis. 26,27 Our results are consistent with the above results, suggesting that SIL1 promotes the growth of breast cancer cells by activating ERK1/2 signaling pathway.…”

Section: Discussionsupporting

confidence: 91%

Nucleotide exchange factor SIL1 promotes the progress of breast cancer cells via regulating the cell cycle and apoptosis

et al. 2019

Science Progress

View full text Add to dashboard Cite

Breast cancer, as one of the most malignant tumors, poses a serious threat to the lives of females. Nucleotide exchange factor SIL1 is an important regulator of endoplasmic reticulum function that might have a specific role in tumor progression. In this study, we aimed to investigate the effect of SIL1 on the proliferation, apoptosis, and metastasis of human breast cancer. SIL1-specific small interfering RNA was transfected into two breast cancer cell lines, MCF7 and MDA-MB-231, to generate SIL1 knockdown cells. Clone formation and Cell Counting Kit-8 assays were performed to determine cell proliferation. Wound healing and transwell assays were used to detect the cell migration and invasion, respectively. Cell cycle and apoptosis were determined by flow cytometry. The messenger RNA and protein levels of target genes were analyzed using quantitative real-time PCR and western blot. According to the results of TCGA and GTEx database analysis, we determined that SIL1 was overexpressed in 1085 breast cancer samples compared with 291 normal samples. Knockdown of SIL1 inhibited the proliferation, migration, and invasion of MCF7 and MDA-MB-231 cells, accordingly. The cell cycle was blocked at the G1 phase following transfection of SIL1-specific small interfering RNA through the inhibition of Cyclin D1, CDK4, and CDK6. SIL1 knockdown induced apoptosis and also promoted the activity of Caspase9 and Bax. Furthermore, SIL1 was able to promote phosphorylation of ERK1/2. Based on these results, SIL1 might act as an oncogene and accelerate the progression of human breast cancer.

show abstract

Section: Discussionsupporting

confidence: 91%

Nucleotide exchange factor SIL1 promotes the progress of breast cancer cells via regulating the cell cycle and apoptosis

et al. 2019

Science Progress

View full text Add to dashboard Cite

show abstract

“…STAT1 is driving the changes in HLA mRNA, protein and cell surface expression after MAPK pathway inhibition (14,15,40). Activated MAPK associated kinases (including ERK1and ALK) directly reduce activated pSTAT1, which promotes proteasomal degradation of pSTAT1 via PIAS1 (46)(47)(48)(49). Hence, inhibition of these pathways should directly increase pSTAT1 output.…”

Section: The Role Of the Jak/stat Pathway In Hla Expression After Mapmentioning

confidence: 99%

ALK and RET Inhibitors Promote HLA Class I Antigen Presentation and Unmask New Antigens within the Tumor Immunopeptidome

Klatt

Bourne

et al. 2019

Cancer Immunology Research

View full text Add to dashboard Cite

T cell immunotherapies are often thwarted by the limited presentation of tumor-specific antigens abetted by the downregulation of human leukocyte antigen (HLA). We showed that drugs inhibiting ALK and RET produced dose-related, increases in cell surface HLA in tumor cells bearing these mutated kinases in vitro and in vivo, as well as elevated transcript and protein expression of HLA and other antigen processing machinery. Subsequent analysis of HLA presented peptides after ALK and RET inhibitor treatment identified large changes in the immunopeptidome with the appearance of hundreds of new antigens, including T cell epitopes associated with impaired peptide processing (TEIPP) peptides. ALK inhibition additionally decreased PD-L1 levels by 75%. Therefore, these oncogenes may enhance cancer formation by allowing tumors to evade the immune system by down regulating HLA expression. Altogether, RET and ALK inhibitors could enhance T cell-based immunotherapies by upregulating HLA, decreasing checkpoint blockade ligands, and revealing new, immunogenic, cancer-associated antigens.

show abstract

“…In patients with spondyloepimetaphyseal dysplasia, MG-132 enhanced caspase-3 and caspase-7 expression, and activated the intrinsic apoptotic pathway to induce apoptosis [44]. In oesophageal squamous cell carcinoma, MG-132 not only activated P-STAT1, but also increased binding to ERK, and induced caspase-3 to increase cell apoptosis [45]. In MM cells, MG-132 inhibited the activation of P-AKT and triggered apoptosis [46].…”

Section: Discussionmentioning

confidence: 99%

HDAC3 Silencing Enhances Acute B Lymphoblastic Leukaemia Cells Sensitivity to MG-132 by Inhibiting the JAK/Signal Transducer and Activator of Transcription 3 Signaling Pathway

Guo

et al. 2020

Chemotherapy

View full text Add to dashboard Cite

Purpose: HDAC3, which is associated with smurf2, has been shown to be associated with poor prognosis in B-ALL. This study examined the efficacy of targeting HDAC3 combined with MG-132 as a possible therapeutic strategy for B-ALL patients. Methods: Real-time PCR and western blot were used to measure the expression of smurf2 and HDAC3 from B-ALL patients bone marrow samples. Sup-B15 and CCRF-SB cells were treated with MG-132, small interfering RNA of smurf2 or HDAC3. A plasmid designed to up-regulate smurf2 expression was transfected into B-ALL cells. Flow cytometry and western blot were used to measure variation due to these treatments in terms of apoptosis and cell cycle arrest. Results: Expression of Smurf2 and HDAC3 mRNA were inversely related in B-ALL patients. Up-regulation of smurf2 or MG-132 influenced HDAC3, further inhibiting the JAK/signal transducer and activator of transcription 3 (STAT3) signal pathway and inducing apoptosis in B-ALL cells. When we treated Sup-B15 and CCRF-SB cells with siHDAC3 and MG-132 for 24 h, silencing HDAC3 enhanced the apoptosis rate induced by MG-132 in B-ALL cells and further inhibited the JAK/STAT3 pathway. Furthermore, MG-132 was observed to cause G2/M phase arrest in B-ALL cells and inhibited the JAK/STAT3 pathway, leading to apoptosis. Conclusions: Silencing of HDAC3 enhanced the sensitivity of B-ALL cells to MG-132. The combination of targeting HDAC3 and MG-132 may provide a new avenue for clinical treatment of acute B lymphocytic leukaemia and improve the poor survival of leukaemia patients.

show abstract

ERK is a negative feedback regulator for IFN-γ/STAT1 signaling by promoting STAT1 ubiquitination

Cited by 29 publications

References 38 publications

Nucleotide exchange factor SIL1 promotes the progress of breast cancer cells via regulating the cell cycle and apoptosis

Nucleotide exchange factor SIL1 promotes the progress of breast cancer cells via regulating the cell cycle and apoptosis

ALK and RET Inhibitors Promote HLA Class I Antigen Presentation and Unmask New Antigens within the Tumor Immunopeptidome

HDAC3 Silencing Enhances Acute B Lymphoblastic Leukaemia Cells Sensitivity to MG-132 by Inhibiting the JAK/Signal Transducer and Activator of Transcription 3 Signaling Pathway

Contact Info

Product

Resources

About