ArticleCancer cell international2019
MKP-4 suppresses hepatocarcinogenesis by targeting ERK1/2 pathway.
Article in Cancer cell international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
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- miR-132-3p Modulates DUSP9-Dependent p38/JNK Signaling Pathways to Enhance Inflammation in the Amnion Leading to Labor.International journal of molecular sciences · 2022Article
- Novel oncogenes and tumor suppressor genes in hepatocellular carcinoma.Liver research (Beijing, China) · 2021Article
- Biphasic Regulation of Mitogen-Activated Protein Kinase Phosphatase 3 in Hypoxic Colon Cancer Cells.Molecules and cells · 2021Article
- DUSP9, a Dual-Specificity Phosphatase with a Key Role in Cell Biology and Human Diseases.International journal of molecular sciences · 2021Review
- GPER-Induced ERK Signaling Decreases Cell Viability of Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- Oleic Acid and Insulin as Key Characteristics of T2D Promote Colorectal Cancer Deterioration in Xenograft Mice Revealed by Functional Metabolomics.Frontiers in oncology · 2021Article
- Dual-specificity Phosphatase 9 protects against Cardiac Hypertrophy by targeting ASK1.International journal of biological sciences · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMitogen-activated protein kinase phosphatases-4 (MKP-4) is reported to exert a prognostic merit in hepatocarcinogenesis. However, the underlying molecular mechanisms have not been clearly defined.
methodsImmunoprecipitation-mass spectrometry (IP-MS) approach was used to identify interactive proteins with MKP-4. Western blot and immunohistochemistry were employed to detect proteins in HCC tissues. Cell counting kit-8, colony formation, Edu incorporation and sphere formation assays were performed to investigate functions of MKP-4/ERK1/2 interaction. Tumor xenografts in nude mice were used to determine effects in vivo.
resultsExtracellular signal-regulated kinase 1 and 2 (ERK1/2) were identified as binding partners of MKP-4. Knockdown of MKP-4 increased cell proliferation and cancer stem cell (CSC) traits while upregulation of MKP-4 or pre-incubation with ERK1/2 inhibition reversed these effects. Mechanistically MKP-4 negatively regulated phosphorylation of ERK1/2 and reduced expressions of CyclinD1 and c-Myc. Both xenograft tumor models and clinical analysis of HCC patients indicated that lower expression of MKP-4 and higher expressions of ERK1/2 were associated with worse prognosis.
conclusionsMKP-4-mediated dephosphorylation of ERK1/2 might serve as a novel tumor-suppressive mechanism and provide a potential therapy for HCC.
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