ArticleJournal of experimental & clinical cancer research : CR2023
Invasive FoxM1 phosphorylated by PLK1 induces the polarization of tumor-associated macrophages to promote immune escape and metastasis, amplified by IFITM1.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Unraveling the connection and pathogenesis of systemic lupus erythematosus and thyroid cancer: integrative meta-analysis, Mendelian randomization, and transcriptomic insights.Clinical rheumatology · 2026Pooled it
- Preclinical Evaluation of Combined Polo-like Kinase 1 Inhibition and Navitoclax in Experimental Models of Lung Cancer.International journal of molecular sciences · 2026Article
- Interferon-induced transmembrane (IFITM) proteins at the tumour-immune interface: A four-axis framework for their context-dependent roles.Clinical and translational medicine · 2026Review
- The Trifecta of Polo-Like Kinases, Cancer, and the Immune System: Emerging Intersections and Therapeutic Insights.Molecular cancer research : MCR · 2026Review
- The flavonoid astragalin induces apoptosis in lung adenocarcinoma and correlates with a prognostic cell cycle gene signature associated with PANoptosis.Translational cancer research · 2026Article
- Integrated bioinformatics and in vitro validation reveal the role of CCT5 in immune infiltration and the Wnt pathway in colon cancer.Discover oncology · 2026Article
- Mitotic Machinery Dysregulation in Lung Cancer: Biological Roles, Therapeutic Targeting, and Combination Strategies.Pharmaceutics · 2026Review
- Cell-type specific activation of the cGAS-STING pathway in tumor immunotherapy: mechanisms and therapeutic implications.Journal of translational medicine · 2026Review
- SHP2 in TAMs promoted the survival of gastric adenocarcinoma via suppressing the P38/ERK1/2/SP1/BRD4/STING induced inflammation and ROS.Frontiers in medicine · 2026Article
- PLK1/FOXM1-associated tumor-cell state and macrophage-related immune features in endometrial cancer.Frontiers in oncology · 2026Article
- Phosphoproteomic analysis in a mouse model reveals ERK signaling as a key modulator of inflammatory response in nasal mucosa associated with childhood allergic rhinitis.Frontiers in immunology · 2026Article
- PLK1 overexpression as a dual-role biomarker and therapeutic vulnerability in pulmonary adenocarcinoma.PeerJ · 2026Article
- Combining sorafenib with spermine and sphingosine synergistically enhances anticancer efficacy by modulating metabolic pathways and gut microbiome in hepatocellular carcinoma.International journal of biological sciences · 2026Article
- Macrophage plasticity in thyroid eye disease: dual effects of inflammation and fibrosis.Frontiers in immunology · 2026Review
- Prognostic role and mutational characteristics of N6-methyladenosine-related genes in lung adenocarcinoma.Oncology letters · 2025Article
- Polo-like kinases as immune modulators: a new frontier in cancer immunotherapy.Trends in cancer · 2025Review
- FOXM1 upregulation, promotes immune escape in gastric cancer through activation of Notch signaling pathway.Molecular and cellular biochemistry · 2025Article
- IFITM1 promotes microglial polarization and NLRP3 inflammasome activation in ischemic stroke through up-regulating c-FOS.Cytotechnology · 2025Article
- Integrating machine learning and genetic evidence to uncover novel gene biomarkers for colorectal cancer diagnosis.Discover oncology · 2025Article
- The multi-target mechanism of action of Selaginella doederleinii Hieron in the treatment of nasopharyngeal carcinoma: a network pharmacology and multi-omics analysis.Scientific reports · 2025Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundUnderstanding the mechanism behind immune cell plasticity in cancer metastasis is crucial for identifying key regulators. Previously we found that mitotic factors regulate epithelial-mesenchymal transition, but how these factors convert to metastatic players in the tumor microenvironment (TME) is not fully understood.
methodsThe clinical importance of mitotic factors was analyzed by heatmap analysis, a KM plot, and immunohistochemistry in lung adenocarcinoma (LUAD) patients. Immunoprecipitation, LC-MS/MS, kinase assay, and site-directed mutagenesis were performed for the interaction and phosphorylation. A tail-vein injection mouse model, Transwell-based 3D culture, microarray analysis, coculture with monocytes, and chromatin immunoprecipitation assays were used to elucidate the function of phosphorylated FoxM1 in metastasis of TME.
resultsThe phosphorylated FoxM1 at Ser25 by PLK1 acquires the reprogramming ability to stimulate the invasive traits in cancer and influence immune cell plasticity. This invasive form of p-FoxM1 upregulates the expression of IL1A/1B, VEGFA, and IL6 by direct activation, recruiting monocytes and promoting the polarization of M2d-like tumor-associated macrophages (TAMs). Upregulation of PD-L1 in LUAD having phosphomimetic FoxM1 facilitates immune evasion. In invasive LUAD with phosphomimetic FoxM1, IFITM1 is the most highly expressed through the activation of the STING-TBK1-IRF3 signaling, which enhances FoxM1-mediated signaling. Clinically, higher expression of FOXM1, PLK1, and IFITM1 is inversely correlated with the survival rate of advanced LUAD patients, providing a promising therapeutic strategy for the treatment of LUAD.
conclusionFoxM1-based therapy would be a potential therapeutic strategy for LUAD to reduce TAM polarization, immune escape, and metastasis, since FoxM1 functions as a genetic reprogramming factor reinforcing LUAD malignancy in the TME.
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