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Oncol."],"abstract":"<jats:p>Vasculogenic mimicry (VM), a micro vessel-like structure formed by the cancer cells, plays a pivotal role in cancer malignancy and progression. Interleukin-1 beta (IL-1\u03b2) is an active pro-inflammatory cytokine and elevated in many tumor types, including breast cancer. However, the effect of IL-1\u03b2 on the VM of breast cancer has not been clearly elucidated. In this study, breast cancer cells (MCF-7 and MDA-MB-231) were used to study the effect of IL-1\u03b2 on the changes that can promote VM. The evidence for VM stimulated by IL-1\u03b2 was acquired by analyzing the expression of VM-associated biomarkers (VE-cadherin, VEGFR-1, MMP-9, MMP-2, c-Fos, and c-Jun) via western blot, immunofluorescent staining, and Immunohistochemistry (IHC). Additionally, morphological evidence was collected via Matrigel-based cord formation assay under normoxic\/hypoxic conditions and microvessel examination through Hematoxylin and Eosin staining (H&amp;amp;E). Furthermore, the STRING and Gene Ontology database was also used to analyze the VM-associated interacting molecules stimulated by IL-\u03b2. The results showed that the expression of VM biomarkers was increased in both MCF-7 and MDA-MB-231 cells after IL-1\u03b2 treatment. The increase in VM response was observed in IL-1\u03b2 treated cells under both normoxia and hypoxia. IL-1\u03b2 also increased the activation of transcription factor AP-1 complex (c-Fos\/c-Jun). The bioinformatics data indicated that p38\/MAPK and PI3K\/Akt signaling pathways were involved in the IL-1\u03b2 stimulation. It was further confirmed by the downregulated expression of VM biomarkers and reduced formation of the intersections upon the addition of the signaling pathway inhibitors. The study suggests that IL-1\u03b2 stimulates the VM and its associated events in breast cancer cells via p38\/MAPK and PI3K\/Akt signaling pathways. Aiming the VM-associated molecular targets promoted by IL-1\u03b2 may offer a novel anti-angiogenic therapeutic strategy to control the aggressiveness of breast cancer cells.<\/jats:p>","DOI":"10.3389\/fonc.2021.618839","type":"journal-article","created":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T06:06:25Z","timestamp":1620972385000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":53,"title":["IL-1\u03b2 Promotes Vasculogenic Mimicry of Breast Cancer Cells Through p38\/MAPK and PI3K\/Akt Signaling Pathways"],"prefix":"10.3389","volume":"11","author":[{"given":"Muhammad Azhar","family":"Nisar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad 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