ArticlePloS one2016
Prognostic and Functional Significance of MAP4K5 in Pancreatic Cancer.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Preliminary examination of noncoding mutations of esophageal squamous cell carcinoma in African Americans.Frontiers in genetics · 2026Article
- MAP4K signaling pathways in cancer: roles, mechanisms and therapeutic opportunities.Experimental & molecular medicine · 2025Review
- In silico identification and biological evaluation of a selective MAP4K4 inhibitor against pancreatic cancer.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Genome-wide CRISPR/Cas9 screens reveal shared and cell-specific mechanisms of resistance to SHP2 inhibition.The Journal of experimental medicine · 2023Article
- Review
- Pancreatic cancer cell-derived exosomes induce epithelial-mesenchymal transition in human pancreatic cancer cells themselves partially via transforming growth factor β1.Medical molecular morphology · 2022Article
- Article
- Identification of a dual TAOK1 and MAP4K5 inhibitor using a structure-based virtual screening approach.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- GCH1-regulated miRNAs are potential targets for microglial activation in neuropathic pain.Bioscience reports · 2021Article
- Pyrrolopyrimidine Bumped Kinase Inhibitors for the Treatment of Cryptosporidiosis.ACS infectious diseases · 2021Article
- Not the comfy chair! Cancer drugs that act against multiple active sites.Expert opinion on therapeutic targets · 2019Review
- Characterization of the Src-regulated kinome identifies SGK1 as a key mediator of Src-induced transformation.Nature communications · 2019Article
- Kinase inhibitors: look beyond the label on the bottle.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- Prognostic Value of mRNA Expression of MAP4K Family in Acute Myeloid Leukemia.Technology in cancer research & treatment · 2019Article
- The Lethality of [Pazopanib + HDAC Inhibitors] Is Enhanced by Neratinib.Frontiers in oncology · 2019Article
- Hippo pathway affects survival of cancer patients: extensive analysis of TCGA data and review of literature.Scientific reports · 2018Review
- Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer.Nature communications · 2017Article
- Prognostic Evaluation of Vimentin Expression in Correlation with Ki67 and CD44 in Surgically Resected Pancreatic Ductal Adenocarcinoma.Gastroenterology research and practice · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesMAP4K5 plays an important role in regulating a range of cellular responses and is involved in Wnt signaling in hematopoietic cells. However, its functions in human malignancies have not been studied. The major objectives of this study are to examine the expression, functions and clinical significance of MAP4K5 in pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND
methodsThe expression levels of MAP4K5, E-cadherin, vimentin, and carboxylesterase 2 (CES2) were examined by immunohistochemistry in 105 PDAC and matched non-neoplastic pancreas samples from our institution. The RNA sequencing data of 112 PDAC patients were downloaded from the TCGA data portal. Immunoblotting and RNA sequencing analysis were used to examine the expression of MAP4K5 and E-cadherin in pancreatic cancer cell lines. The effect of knockdown MAP4K5 using siRNA on the expression of CDH1 and vimentin were examined by Real-time RT-PCR in Panc-1 and AsPC-1 cells. Statistical analyses were performed using IBM SPSS Statistics.
resultsMAP4K5 protein is expressed at high levels specifically in the pancreatic ductal cells of 100% non-neoplastic pancreas samples, but is decreased or lost in 77.1% (81/105) of PDAC samples. MAP4K5-low correlated with the loss of E-cadherin (P = 0.001) and reduced CES2 expression (P = 0.002) in our patient populations. The expression levels of MAP4K5 mRNA directly correlated with the expression levels of CDH1 mRNA (R = 0.2490, P = 0.008) in the second cohort of 112 PDAC patients from The Cancer Genome Atlas (TCGA) RNA-seq dataset. Similar correlations between the expression of MAP4K5 and E-cadherin were observed both at protein and mRNA levels in multiple pancreatic cancer cell lines. Knockdown MAP4K5 led to decreased CDH1 mRNA expression in Panc-1 and AsPC-1 cells. MAP4K5-low correlated significantly with reduced overall survival and was an independent prognosticator in patients with stage II PDAC.
conclusionsMAP4K5 expression is decreased or lost in majority of PDACs. The strong associations between low MAP4K5 expression and loss of E-cadherin, reduced CES2 expression and decreased overall survival may suggest an important role of MAP4K5 in epithelial-to-mesenchymal transition, chemotherapy resistance and tumor progression in pancreatic cancer. Targeting impaired MAP4K5 signaling may represent a new therapeutic strategy for pancreatic cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.