Unraveling the role of myeloid-derived ROS on EMT in metastasizing cancer

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dc.contributor.authorJohnsson, Olivia
dc.contributor.departmentChalmers tekniska högskola / Institutionen för life sciencessv
dc.contributor.departmentChalmers University of Technology / Department of Life Sciencesen
dc.contributor.examinerKarlsson-Bengtsson, Anna
dc.contributor.supervisorMartner , Anna
dc.contributor.supervisorKaya, Mustafa
dc.date.accessioned2024-06-18T08:44:12Z
dc.date.available2024-06-18T08:44:12Z
dc.date.issued2024
dc.date.submitted
dc.description.abstractEpithelial-to-mesenchymal transition (EMT) allows epithelial cells in primary cancer tumors to adopt a more mesenchymal morphology, thus facilitating metastasis. This process is influenced by a multitude of transcription factors and pathways, including the p53 and NF-κB signaling pathways. Myeloid cells in the tumor microenvironment produce reactive oxygen species (ROS) via the NOX2 enzyme, and while inflammation previously has been linked to EMT, the role of myeloid-derived ROS remains unknown. The aim of this thesis was to understand the intracellular pathways connecting myeloidderived ROS and EMT in breast cancer. To this end, breast cancer cell lines of varying differentiation grade were treated with the ROS hydrogen peroxide in combination with intracellular pathway activators or inhibitors. Effects on EMT-related gene and protein expression were measured using quantitative PCR and western blot, respectively. It was observed that the SNAI family of EMT transcription factors was induced by the redox regulator Nrf2, while ROS-induced SERPINE1 was regulated by p53. SERPINE1 encodes plasminogen activator inhibitor-1 (PAI-1), a biomarker in several cancers, which has also been linked to EMT and inflammation. The results were validated using CRISPR-Cas9 mediated knockout of the TP53 gene. In addition, bioinformatic and in silico analyses of publicly available datasets corroborated these results. The links between H2O2 and EMT in breast cancer implied by the results of this thesis show potential targets for limiting EMT in breast cancer. Further studies are necessary to fully understand the involved mechanisms and their regulation.
dc.identifier.coursecodeBBTX60
dc.identifier.urihttp://hdl.handle.net/20.500.12380/307903
dc.language.isoeng
dc.setspec.uppsokLifeEarthScience
dc.subjectEpithelial-to-mesenchymal transition
dc.subjectReactive oxygen species
dc.subjectMyeloid cells
dc.subjectMetastasis
dc.subjectBreast cancer.
dc.titleUnraveling the role of myeloid-derived ROS on EMT in metastasizing cancer
dc.type.degreeExamensarbete för masterexamensv
dc.type.degreeMaster's Thesisen
dc.type.uppsokH
local.programmeBiotechnology (MPBIO), MSc
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