Invasive FoxM1 phosphorylated by PLK1 induces the polarization of tumor-associated macrophages to promote immune escape and metastasis, amplified by IFITM1
DC Field | Value | Language |
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dc.contributor.author | Xu, Rong | - |
dc.contributor.author | Lee, Young-Joo | - |
dc.contributor.author | Kim, Chang-Hyeon | - |
dc.contributor.author | Min, Ga-Hong | - |
dc.contributor.author | Kim, Yeo-Bin | - |
dc.contributor.author | Park, Jung-Won | - |
dc.contributor.author | Kim, Dae-Hoon | - |
dc.contributor.author | Kim, Jung-Hyun | - |
dc.contributor.author | Yim, Hyungshin | - |
dc.date.accessioned | 2023-11-24T02:30:17Z | - |
dc.date.available | 2023-11-24T02:30:17Z | - |
dc.date.issued | 2023-11 | - |
dc.identifier.issn | 1756-9966 | - |
dc.identifier.issn | 1756-9966 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/115640 | - |
dc.description.abstract | Background: Understanding 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. Methods: The 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. Results: The 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. Conclusion: FoxM1-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. © 2023, The Author(s). | - |
dc.format.extent | 25 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | BMC | - |
dc.title | Invasive FoxM1 phosphorylated by PLK1 induces the polarization of tumor-associated macrophages to promote immune escape and metastasis, amplified by IFITM1 | - |
dc.type | Article | - |
dc.publisher.location | 영국 | - |
dc.identifier.doi | 10.1186/s13046-023-02872-1 | - |
dc.identifier.scopusid | 2-s2.0-85176397055 | - |
dc.identifier.wosid | 001102253600002 | - |
dc.identifier.bibliographicCitation | Journal of Experimental & Clinical Cancer Research, v.42, no.1, pp 1 - 25 | - |
dc.citation.title | Journal of Experimental & Clinical Cancer Research | - |
dc.citation.volume | 42 | - |
dc.citation.number | 1 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 25 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | EPITHELIAL-MESENCHYMAL TRANSITION | - |
dc.subject.keywordPlus | TRANSCRIPTION FACTOR | - |
dc.subject.keywordPlus | TGF-BETA | - |
dc.subject.keywordPlus | CANCER | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | MIGRATION | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | CARCINOMA | - |
dc.subject.keywordPlus | GENES | - |
dc.subject.keywordPlus | PROLIFERATION | - |
dc.subject.keywordAuthor | FoxM1 | - |
dc.subject.keywordAuthor | Invasiveness | - |
dc.subject.keywordAuthor | Phosphorylation | - |
dc.subject.keywordAuthor | PLK1 | - |
dc.subject.keywordAuthor | Tumor-associated macrophages | - |
dc.identifier.url | https://jeccr.biomedcentral.com/articles/10.1186/s13046-023-02872-1 | - |
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