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MAP2K1 expression
i
Other names: MAP2K1, MAPKK1, MEK1, PRKMK1, Mitogen-activated protein kinase kinase 1
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Entrez ID:
2ms
Inhibition of the long non-coding RNA MALAT1 downregulates MAP2K1 to suppress the progression of hypopharyngeal squamous cell carcinoma. (PubMed, Biomol Biomed)
Additionally, it induced apoptosis, affected the cell cycle, and inhibited tumor growth. Our study uniquely demonstrates that targeting MALAT1 significantly impedes HSCC progression by downregulating its novel downstream target, MAP2K1, offering new insights into potential therapeutic strategies.
Journal
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MAP2K1 (Mitogen-activated protein kinase kinase 1) • MALAT1 (Metastasis associated lung adenocarcinoma transcript 1)
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MAP2K1 expression
6ms
Role of MEK1 and DIAPH3 expression in colorectal adenoma-carcinoma sequence. (PubMed, Tumour Biol)
This co- expression suggests a possible synergistic effect of MEK1 and DIAPH-3 in colorectal ACS. Further large-scale studies are required to investigate the potential functional aspects of MEK1 and DIAPH3 in ACS and their involvement in tumor initiation and the metastatic process.
Journal
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MAP2K1 (Mitogen-activated protein kinase kinase 1) • DIAPH3 (Diaphanous Related Formin 3)
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MAP2K1 overexpression • MAP2K1 expression
7ms
Reversine inhibits proliferation and induces apoptosis of human osteosarcoma cells through targeting MEK1. (PubMed, J Bone Oncol)
Western blot results show the regulation of MEK1 and ERK1/2 by reversine was not consistent in different osteosarcoma cell lines, but we found that reversine significantly inhibited the protein expression of MEK1 in MNNG/HOS, U-2 OS and MG-63. All these suggested that reversine can exert its anti-tumor effect by targeting the expression of MEK1.
Journal
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PTEN (Phosphatase and tensin homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • CDH1 (Cadherin 1) • RAC1 (Rac Family Small GTPase 1) • RHOA (Ras homolog family member A) • VIM (Vimentin) • CDH2 (Cadherin 2) • CDC42 (Cell Division Cycle 42) • PTK2 (Protein Tyrosine Kinase 2)
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CDH1 expression • VIM expression • MAP2K1 expression
9ms
The effect of STAT1, miR-99b, and MAP2K1 in alcoholic liver disease (ALD) mouse model and hepatocyte. (PubMed, Aging (Albany NY))
In conclusion, we identified the correlation and effect of STAT1, miR-99b, and MAP2K1 in ALD mouse model and hepatocyte. STAT1, miR-99b, and MAP2K1 may serve as potential therapeutic target of ALD.
Preclinical • Journal
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MAP2K1 (Mitogen-activated protein kinase kinase 1) • STAT1 (Signal Transducer And Activator Of Transcription 1) • MIR99B (MicroRNA 99b)
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MAP2K1 overexpression • MAP2K1 expression
11ms
MicroRNA miR-212-5p Regulates the MEK/ERK Signaling Pathway by Targeting A-Raf proto-oncogene serine/threonine-protein kinase (ARAF) to Regulate Cowshed PM-Induced NR8383 Apoptosis. (PubMed, Toxics)
The miR-212-5p mimic group showed an up-regulation of Bax and cleaved Caspase 3 expression but decreased Bcl2 expression compared to the NC group, and overexpression of ARAF up-regulated the expression of p-MEK1/2 and p-ERK1/2 and simultaneously reversed the above phenomena. miR-212-5p targets ARAF to affect the cowshed PM-induced apoptosis through the MEK/ERK signaling pathway, providing a potential target for relevant farming industry and pathology studies.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3) • ARAF (A-Raf Proto-Oncogene)
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BCL2 expression • MAP2K1 expression
1year
Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: A Report from the Children's Oncology Group (ASH 2023)
Upfront therapies typically include high-dose cytarabine or azacitidine, but the only definitive treatment is hematopoietic stem cell transplantation (HSCT). We conducted an open label, phase 2 trial of trametinib in children with relapsed or refractory JMML. This is the first completed study of a MEK inhibitor in any hematologic malignancy in children. The trial met its primary objective and demonstrated a 50% objective response rate with 70% of patients bridging to a successful HSCT or completing the maximum 12 cycles permitted on study.
Clinical
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KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
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KRAS mutation • NRAS mutation • NF1 mutation • RAS mutation • CBL mutation • MAP2K1 expression
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Mekinist (trametinib) • cytarabine • azacitidine
over1year
Investigating the effect of MAP2K1 gene (MEK1) in MAPK pathway in the induction of adult T-cell leukemia/lymphoma (ATLL). (PubMed, Iran J Microbiol)
The mutational sequencing analysis showed nucleotide 212 (S→R) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database. These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role.
Journal
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MAP2K1 (Mitogen-activated protein kinase kinase 1)
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MAP2K1 expression
over1year
TRIM29 facilitates proliferation and malignancy of cholangiocarcinoma cells by activating MAPK and β-catenin pathways. (PubMed, Environ Toxicol)
TRIM29 plays an oncogenic role in cholangiocarcinoma. It may promote the malignancy of cholangiocarcinoma via inducing the activation of the MAPK and β-catenin pathways. Thus, TRIM29 may aid in the creation of innovative treatment strategies for cholangiocarcinoma.
Journal
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MAP2K1 (Mitogen-activated protein kinase kinase 1) • CDH1 (Cadherin 1) • CD33 (CD33 Molecule) • SOX2 • VIM (Vimentin) • CDH2 (Cadherin 2) • NANOG (Nanog Homeobox)
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CDH1 expression • VIM expression • MAP2K1 expression
over1year
Phosphatase regenerating liver 3 participates in Integrinβ1/FAK-Src/MAPK signaling pathway and contributes to the regulation of malignant behaviors in hepatocellular carcinoma cells. (PubMed, J Gastrointest Oncol)
Mechanically, PRL-3 plays a critical role in HCC invasive and metastasis via Integrinβ1/FAK-Src/RasMAPK signaling. Validation of PRL-3 as a clinical prediction marker in HCC warrants further research.
Journal
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MMP9 (Matrix metallopeptidase 9) • PTP4A3 (Protein Tyrosine Phosphatase 4A3)
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MAP2K1 expression
almost2years
Chinese Herbal Medicine 'Diwu' Suppresses Myeloma Bone Disease Via ERK/MAPK Signaling Pathway By Targeting CCL3 (ASH 2022)
Conclusion s : Altogether, our results demonstrated that effective extract of Chinese herbal medicine 'Diwu' could simultaneously inhibit myeloma cells and suppress osteoclast formation, indicating an important role of 'Diwu' in regulating BM microenvironment. It is possible to translate 'Diwu' into clinical application as an oral agent for myeloma bone disease.Key words:'Diwu'; Myeloma Bone Disease; Bone Marrow Microenvironment; CCL3; ERK/MAPK
IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • CSF1 (Colony stimulating factor 1) • CASP3 (Caspase 3)
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BCL2 expression • MAP2K1 expression
2years
Ribosomal protein RPL5 regulates colon cancer cell proliferation and migration through MAPK/ERK signaling pathway. (PubMed, BMC Mol Cell Biol)
RPL5 promoted colon cell proliferation and migration, at least in part, by activating the MAPK/ERK signaling pathway, which may serve as a novel therapeutic target for cancers in which MAPK/ERK signaling is a dominant feature.
Journal
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • FOXO3 (Forkhead box O3) • RPL5 (Ribosomal Protein L5)
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MYC expression • RPL5 expression • MAP2K1 expression
over2years
Chinese herbal medicine ‘Diwu’ suppresses myeloma bone disease via ERK/MAPK signaling pathway by targeting CCL3 (IMW 2022)
Altogether, our results demonstrated that effective extract of Chinese herbal medicine ‘Diwu’ could simultaneously inhibit myeloma cells and suppress osteoclast formation, indicating an important role of ‘Diwu’ in regulating BM microenvironment. It is possible to translate ‘Diwu’ into clinical application as an oral agent for myeloma bone disease.
IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • CSF1 (Colony stimulating factor 1) • CASP3 (Caspase 3)
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BCL2 expression • MAP2K1 expression
over2years
KIF22 Promotes Development of Pancreatic Cancer by Regulating the MEK/ERK/P21 Signaling Axis. (PubMed, Biomed Res Int)
According to our findings, KIF22 is highly expressed in pancreatic cancer and demonstrates a poor clinical prognosis. It regulates the cell cycle via the MEK/ERK/P21 signaling axis and promotes the development of pancreatic cancer.
Journal
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MAP2K1 (Mitogen-activated protein kinase kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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MAP2K1 mutation • MAP2K1 expression
over2years
Altersolanol B, a fungal tetrahydroanthraquinone, inhibits the proliferation of estrogen receptor-expressing (ER+) human breast adenocarcinoma by modulating PI3K/AKT, p38/ERK MAPK and associated signaling pathways. (PubMed, Chem Biol Interact)
Our preliminary study suggested that the THAQ pharmacophore, with its disrupted conjugated ring system and relative redox inactivity, may possess greater mechanistic advantage against ER + breast cancer when compared to the fully conjugated ring systems of the anthraquinone that possess intrinsic redox activity and DNA interacting ability. This study supports the continued investigation of THAQs as lead molecules in anticancer drug discovery and development.
Journal • PARP Biomarker • IO biomarker
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ER (Estrogen receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • TNFA (Tumor Necrosis Factor-Alpha) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • HMOX1 (Heme Oxygenase 1) • BAX (BCL2-associated X protein) • CDK2 (Cyclin-dependent kinase 2) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • CASP9 (Caspase 9) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4)
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ER positive • ER negative • BCL2 expression • TP53 expression • ER expression • BAX expression • MAP2K1 expression
3years
Inflammatory conversion of quiescent osteoblasts by metastatic breast cancer cells through pERK1/2 aggravates cancer-induced bone destruction. (PubMed, Bone Res)
Trametinib, an FDA-approved MEK inhibitor, not only reduced breast cancer-induced bone destruction but also dramatically reduced cancer growth in bone by inhibiting the inflammatory skeletal microenvironment. Taken together, these findings suggest that ERK1/2 activation in both breast cancer cells and osteoblasts is required for osteolytic breast cancer-induced inflammatory osteolysis and that ERK1/2 pathway inhibitors may represent a promising adjuvant therapy for patients with aggressive osteolytic breast cancers by altering the shared cancer and bone microenvironment.
Journal
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MAP2K1 (Mitogen-activated protein kinase kinase 1)
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MAP2K1 expression
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Mekinist (trametinib)
3years
Integrative pan-cancer analysis of MEK1 aberrations and the potential clinical implications. (PubMed, Sci Rep)
Mesothelioma (MESO) has the second highest alterations but has no therapy targets. This study provided a great and detailed interpretation of MEK1 expression, alterations and clinical implications in 32 types of cancer and reminded us to fill the gap in MEK1 research from a new perspective.
Clinical • Journal • Pan tumor
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MAP2K1 (Mitogen-activated protein kinase kinase 1)
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MAP2K1 expression
over3years
The newly identified MEK1 tyrosine phosphorylation target MACC1 is druggable by approved MEK1 inhibitors to restrict colorectal cancer metastasis. (PubMed, Oncogene)
Targeting MEK1 by RNAi or clinically applicable MEK1 inhibitors AZD6244 and GSK1120212 reduces MACC1 tyrosine phosphorylation and restricts MACC1-induced metastasis formation in mice. This fundamental finding opens new therapeutic options for targeting the MEK1/MACC1 axis as novel vulnerability in patients at high risk for metastasis. This might be extended from CRC to further solid tumor entities.
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase) • MACC1 (MET Transcriptional Regulator MACC1)
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MET expression • MAP2K1 expression
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Mekinist (trametinib) • Koselugo (selumetinib)
over3years
HDAC8 Activates AKT through Upregulating PLCB1 and Suppressing DESC1 Expression in MEK1/2 Inhibition-Resistant Cells. (PubMed, Cells)
By using inhibitors, small interference RNAs and/or expression vectors, we found that the inhibition of HDAC8 suppressed PLCB1 expression and induced DESC1 expression in the resistant cells, which led to the inhibition of AKT and re-sensitization to LT and MEK1/2 inhibition. These results suggest that targeting PLCB1 and DESC1 is a novel strategy for inhibiting the resistance to MEK1/2 inhibition.
Journal
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BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
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BRAF mutation • NRAS mutation • MAP2K1 expression
over3years
[VIRTUAL] Characterization of trametinib combined with venetoclax in acute myeloid leukemia (AML) treatment (AACR 2021)
Furthermore, we demonstrated that while venetoclax treatment increased protein levels of MCL1 in MOLM13 AML cells, combining trametinib with venetoclax reduced MCL1 levels. In summary, we demonstrate efficacy of trametinib and venetoclax combination in AML and propose mechanisms underlying the synergistic relationship of this drug combination.
IO biomarker
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KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • MCL1 (Myeloid cell leukemia 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
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TP53 mutation • KRAS mutation • SRSF2 mutation • MAP2K1 expression
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Venclexta (venetoclax) • Mekinist (trametinib)
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