ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
MAP4K4 promotes epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Methodological Pitfalls in Endometriosis Biospecimen Research: Lessons From MAP4K4 Expression Studies.FASEB bioAdvances · 2026Article
- RNA-binding protein hnRNPD induces epithelial-mesenchymal transition in Wilms' tumor via facilitating MAP4K4 mRNA stability.Molecular genetics and genomics : MGG · 2026Article
- NF-κB signaling in hepatocellular carcinoma: Mechanisms of tumor progression, immune evasion, and therapeutic resistance.Translational oncology · 2026Review
- Multidimensional outlook on the pathophysiology of cervical cancer invasion and metastasis.Molecular and cellular biochemistry · 2023Review
- MAP4K4 promotes ovarian cancer metastasis through diminishing ADAM10-dependent N-cadherin cleavage.Oncogene · 2023Article
- Review
- PCB: A pseudotemporal causality-based Bayesian approach to identify EMT-associated regulatory relationships of AS events and RBPs during breast cancer progression.PLoS computational biology · 2023Article
- Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer.Genes · 2022Article
- Dissecting novel mechanisms of hepatitis B virus related hepatocellular carcinoma using meta-analysis of public data.World journal of gastrointestinal oncology · 2022Article
- Apigenin Inhibits the Growth of Hepatocellular Carcinoma Cells by Affecting the Expression of microRNA Transcriptome.Frontiers in oncology · 2021Article
- Neratinib degrades MST4 via autophagy that reduces membrane stiffness and is essential for the inactivation of PI3K, ERK1/2, and YAP/TAZ signaling.Journal of cellular physiology · 2020Article
- Selective protection of human cardiomyocytes from anthracycline cardiotoxicity by small molecule inhibitors of MAP4K4.Scientific reports · 2020Article
- Review
- Targeted genomic CRISPR-Cas9 screen identifies MAP4K4 as essential for glioblastoma invasion.Scientific reports · 2019Article
- MicroRNA profiling of pancreatic ductal adenocarcinoma (PDAC) reveals signature expression related to lymph node metastasis.Oncotarget · 2019Article
- Prognostic Value of mRNA Expression of MAP4K Family in Acute Myeloid Leukemia.Technology in cancer research & treatment · 2019Article
- Chemotherapy-inducedBioscience reports · 2018Article
- The Misshapen kinase regulates the size and stability of the germline ring canals in the Drosophila egg chamber.Developmental biology · 2018Article
- Transformation-induced stress at telomeres is counteracted through changes in the telomeric proteome including SAMHD1.Life science alliance · 2018Article
- High expression of Rap2A is associated with poor prognosis of patients with hepatocellular carcinoma.International journal of clinical and experimental pathology · 2017Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our previous study has reported that mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) regulates the growth and survival of hepatocellular carcinoma (HCC) cells. This study was undertaken to explore the roles of MAP4K4 in the epithelial-mesenchymal transition (EMT) and metastasis in HCC. Effects of overexpression and knockdown of MAP4K4 on the migration, invasion, and EMT of HCC cells were examined. The in vivo role of MAP4K4 in lung metastasis of HCC was determined in nude mice. The relationship between MAP4K4 expression and EMT in human HCC specimens was determined by immunohistochemistry. MAP4K4 overexpression significantly enhanced the migration and invasion of MHCC-97L HCC cells, whereas MAP4K4 silencing hindered the migration and invasion of MHCC-97H HCC cells. MAP4K4-overexpressing cells undergo EMT, which was accompanied by downregulation of E-cadherin and upregulation of vimentin. In contrast, MAP4K4 silencing caused a reversion from a spindle morphology to cobblestone-like morphology and induction of E-cadherin and reduction of vimentin. Pretreatment with chemical inhibitors of JNK and NF-κB abolished MAP4K4-mediated migration, invasion, and regulation of EMT markers in MHCC-97L cells. Ectopic expression of MAP4K4 promoted and knockdown of MAP4K4 inhibited lung metastasis of HCC, which was associated with regulation of JNK and NF-κB signaling and EMT markers. High MAP4K4 immunoreactivity was inversely correlated with E-cadherin and was positively correlated with vimentin, phospho-JNK, and phospho-NF-κB in HCC specimens. Taken together, MAP4K4 promotes the EMT and invasiveness of HCC cells largely via activation of JNK and NF-κB signaling.
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