ArticleMolecular cancer2018
PKN2 in colon cancer cells inhibits M2 phenotype polarization of tumor-associated macrophages via regulating DUSP6-Erk1/2 pathway.
Article in Molecular cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.
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Who cites it
94 citing papers in PubMed, 1 synthesis or guideline pooled it, 177 citations in OpenAlex.
- EPSTI1 as an immune biomarker predicts the prognosis of patients with stage III colon cancer.Frontiers in immunology · 2022Pooled it
- TMC7 promotes colorectal cancer metastasis via inhibition of PKN2 and regulation of hypoxia-adaptive responses.Translational oncology · 2026Article
- Implications of Rho GTPase signaling in cancer immunotherapy.Biochemical Society transactions · 2026Review
- Decoding the shared genetic liability of lower respiratory tract infections via genomic structural equation modeling.BMC pulmonary medicine · 2026Article
- SPP1+ macrophages contribute to silica-induced pulmonary inflammation and fibrosis via the ERK/JNK signaling pathway.American journal of respiratory cell and molecular biology · 2026Article
- MM-derived exosomes promote M2 macrophage polarization and immunosuppressive microenvironment: therapeutic opportunities.Blood cancer journal · 2026Article
- RNF34 restrains endometriosis through SREBP1-dependent metabolic-immune crosstalk.Cellular and molecular life sciences : CMLS · 2026Article
- Macrophage-Specific Loss of Stearoyl-CoA Desaturase 1 Promotes Colon Cancer by Enhancing M2 TAM Polarization.Cancer science · 2026Article
- A prognostic model based on ScissorTranslational cancer research · 2026Article
- Abnormal glycosylation of MUC20 mediates TAM polarization and promotes immune escape in colorectal cancer.Communications biology · 2026Article
- Migration and invasion inhibitory protein inhibits M2 macrophage polarization to suppress colorectal cancer progression through the STING-NFκB2-IL10 axis.Cancer biology & medicine · 2026Article
- Hypoxic tumor microenvironment and immune cell dynamics: From metabolic reprogramming to therapeutic innovation.Iranian journal of basic medical sciences · 2026Review
- PSMD2-Mediated MAPK Signaling Promotes Bladder Cancer Development and Immune Microenvironment Remodeling.Oncology research · 2026Article
- The resilient subset: cancer stem cells at the core of immunotherapy resistance.Immunotherapy advances · 2026Review
- Unravelling the Phosphorylation Landscape of Anthrax Toxin Receptor 1: Mechanisms and Functional Insights Through Phosphoproteomic Data Integration.The protein journal · 2025Article
- Endometrial Mesenchymal Stem Cell-Derived Exosomal miR-4669 Promotes EMT in Adenomyosis by Inducing M2 Macrophage Polarization via the DUSP6/ERK Pathway.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Macrophages: Subtypes, Distribution, Polarization, Immunomodulatory Functions, and Therapeutics.MedComm · 2025Review
- PKN2 Inhibits VEGFA and bFGF-Mediated Angiogenesis by Targeting HIF-1α in Colon Cancer.The Kaohsiung journal of medical sciences · 2025Article
- Regulation and Function of Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): The Role of the SRIF System in Macrophage Regulation.International journal of molecular sciences · 2025Review
- Tumor-associated macrophages remodel the suppressive tumor immune microenvironment and targeted therapy for immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
34 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundProtein kinase N2 (PKN2) is a PKC-related serine/threonine-protein kinase. PKN2 is required for tumor cell migration, invasion and apoptosis. However, the functional role of PKN2 in regulating tumor associated macrophages (TAMs) polarization in colon cancer has never been reported.
methodsPKN2 expression in human colon cancer tissues was examined with immunohistochemistry (IHC). M1/M2 macrophage signatures were evaluated by RT-PCR, IHC and flow cytometry. The effects of PKN2 on tumor growth and TAM polarization were investigated both in vitro and in vivo. PKN2 targeted cytokines/pathway were analyzed by gene expression analysis and further confirmed by PCR, luciferase assay or western blot. Correlations between PKN2 and transcriptional factors for IL4 and IL10 were confirmed by ChIP-qPCR. The catalytic activities of PKN2 and DUSP6 were determined by kinase activity assay. Interactions between PKN2 and DUSP6 were confirmed by Co-IP.
resultsThe expression of PKN2 in colon cancer cells predicted a favorable prognosis and was associated with low M2 macrophage content in human colon cancer tissues. PKN2 inhibited tumor growth in mice xenograft model and inhibited M2 phenotype polarization both in vitro and in vivo. Mechanistically, PKN2 suppresses the expression of IL4 and IL10 from colon cancer cells by inhibiting Erk1/2 phosphorylation, which is required for phosphorylation and binding of CREB and Elk-1 to the promoters of IL4 and IL10. DUSP6, which is phosphorylated and activated through direct association with PKN2, suppresses Erk1/2 activation.
conclusionsThe expression of PKN2 in colon cancer cells suppresses tumor associated M2 macrophage polarization and tumor growth. Targeting PKN2 signaling pathway may provide a potential therapeutic strategy for colon cancer.
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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 Socratic graph.