{"id":{"repo_id":"milano","oai_identifier":"oai:air.unimi.it:2434/1151635"},"canonical_url":"https://search.dev.ndltd.org/etd/milano/oai:air.unimi.it:2434/1151635","repository":{"repo_id":"milano","name":"Università degli Studi di Milano","base_url":"https://air.unimi.it/oai/request"},"display":{"title":"PRUNE_1 INVOLMENT IN TNBC ENHANCING CANCER METABOLISM","abstract":"Tumor initiation and progression depend on the metabolic reprogramming of cancer cells to meet heightened energy and biosynthetic demands. Triple-Negative Breast Cancer (TNBC), characterized by the absence of hormone and HER2 receptors, exhibits high glycolytic and oxidative phosphorylation (OXPHOS) activity, contributing to poor prognosis and metastasis. The ATP5A1 protein, a key component of mitochondrial ATP synthase, plays a central role in energy metabolism and is linked to cancer-specific metabolic alterations, including the Warburg effect. Polyphosphates (PolyP) emerge as critical modulators of ATP synthesis through their degradation by Prune1, which facilitates ADP-ATP conversion and supports mitochondrial function under stress. Prune1 overexpression is associated with metastasis, epithelial-mesenchymal transition (EMT), and poor prognosis in cancers. It modulates intracellular pathways, including WNT and TGF-β signaling, through interactions with cytoskeleton proteins and kinases. Using a genetically engineered mouse model (GEMM) of metastatic TNBC (MMTV-Prune1/Wnt1), Prune1 was found to enhance glycolysis and OXPHOS, promoting lung metastases by inhibiting GSK-3 activity. Prune1's mitochondrial localization and interaction with ATP5A1 highlight its role in OXPHOS-mediated ATP production. The Prune1 inhibitor (LEO-AA7.5(S)T) was shown to impair tumor metastasis, enhance cell adhesion, and inhibit metabolic reprogramming by activating GSK-3 and NDPK-A. These findings underscore Prune1 as a potential therapeutic target for high-risk metastatic TNBC and cancers with altered glycolysis and OXPHOS pathways.","abstract_html":"Tumor initiation and progression depend on the metabolic reprogramming of cancer cells to meet heightened energy and biosynthetic demands. Triple-Negative Breast Cancer (TNBC), characterized by the absence of hormone and HER2 receptors, exhibits high glycolytic and oxidative phosphorylation (OXPHOS) activity, contributing to poor prognosis and metastasis. The ATP5A1 protein, a key component of mitochondrial ATP synthase, plays a central role in energy metabolism and is linked to cancer-specific metabolic alterations, including the Warburg effect. Polyphosphates (PolyP) emerge as critical modulators of ATP synthesis through their degradation by Prune1, which facilitates ADP-ATP conversion and supports mitochondrial function under stress. Prune1 overexpression is associated with metastasis, epithelial-mesenchymal transition (EMT), and poor prognosis in cancers. It modulates intracellular pathways, including WNT and TGF-β signaling, through interactions with cytoskeleton proteins and kinases. Using a genetically engineered mouse model (GEMM) of metastatic TNBC (MMTV-Prune1/Wnt1), Prune1 was found to enhance glycolysis and OXPHOS, promoting lung metastases by inhibiting GSK-3 activity. Prune1's mitochondrial localization and interaction with ATP5A1 highlight its role in OXPHOS-mediated ATP production. The Prune1 inhibitor (LEO-AA7.5(S)T) was shown to impair tumor metastasis, enhance cell adhesion, and inhibit metabolic reprogramming by activating GSK-3 and NDPK-A. These findings underscore Prune1 as a potential therapeutic target for high-risk metastatic TNBC and cancers with altered glycolysis and OXPHOS pathways.","abstract_has_math":false,"creators":["ASADZADEH, FATEMEH"],"institution":"Università degli Studi di Milano","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["supervisor: M. Zollo ; internal advisor: D. Grieco ; external advisor: J. P Sleeman","F. Asadzadeh"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-02-21","date_published":"2025-02-21","updated_at":"2026-07-27T20:19:00Z","subjects":["Settore MEDS-09/A - Oncologia medica"],"languages":["eng"],"rights":["info:eu-repo/semantics/embargoedAccess"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2434/1151635","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["supervisor: M. Zollo ; internal advisor: D. Grieco ; external advisor: J. P Sleeman","F. 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Triple-Negative Breast Cancer (TNBC), characterized by the absence of hormone and HER2 receptors, exhibits high glycolytic and oxidative phosphorylation (OXPHOS) activity, contributing to poor prognosis and metastasis. The ATP5A1 protein, a key component of mitochondrial ATP synthase, plays a central role in energy metabolism and is linked to cancer-specific metabolic alterations, including the Warburg effect. Polyphosphates (PolyP) emerge as critical modulators of ATP synthesis through their degradation by Prune1, which facilitates ADP-ATP conversion and supports mitochondrial function under stress. Prune1 overexpression is associated with metastasis, epithelial-mesenchymal transition (EMT), and poor prognosis in cancers. It modulates intracellular pathways, including WNT and TGF-β signaling, through interactions with cytoskeleton proteins and kinases. Using a genetically engineered mouse model (GEMM) of metastatic TNBC (MMTV-Prune1/Wnt1), Prune1 was found to enhance glycolysis and OXPHOS, promoting lung metastases by inhibiting GSK-3 activity. Prune1's mitochondrial localization and interaction with ATP5A1 highlight its role in OXPHOS-mediated ATP production. The Prune1 inhibitor (LEO-AA7.5(S)T) was shown to impair tumor metastasis, enhance cell adhesion, and inhibit metabolic reprogramming by activating GSK-3 and NDPK-A. These findings underscore Prune1 as a potential therapeutic target for high-risk metastatic TNBC and cancers with altered glycolysis and OXPHOS pathways."]},{"key":"dc:title","label":"Title","values":["PRUNE_1 INVOLMENT IN TNBC ENHANCING CANCER METABOLISM"]}]}],"canonical_facts":{"dc:contributor":["supervisor: M. Zollo ; internal advisor: D. Grieco ; external advisor: J. P Sleeman","F. Asadzadeh"],"dc:creator":["ASADZADEH, FATEMEH"],"dc:date":["2025-02-21"],"dc:description":["Tumor initiation and progression depend on the metabolic reprogramming of cancer cells to meet heightened energy and biosynthetic demands. Triple-Negative Breast Cancer (TNBC), characterized by the absence of hormone and HER2 receptors, exhibits high glycolytic and oxidative phosphorylation (OXPHOS) activity, contributing to poor prognosis and metastasis. The ATP5A1 protein, a key component of mitochondrial ATP synthase, plays a central role in energy metabolism and is linked to cancer-specific metabolic alterations, including the Warburg effect. Polyphosphates (PolyP) emerge as critical modulators of ATP synthesis through their degradation by Prune1, which facilitates ADP-ATP conversion and supports mitochondrial function under stress. Prune1 overexpression is associated with metastasis, epithelial-mesenchymal transition (EMT), and poor prognosis in cancers. It modulates intracellular pathways, including WNT and TGF-β signaling, through interactions with cytoskeleton proteins and kinases. Using a genetically engineered mouse model (GEMM) of metastatic TNBC (MMTV-Prune1/Wnt1), Prune1 was found to enhance glycolysis and OXPHOS, promoting lung metastases by inhibiting GSK-3 activity. Prune1's mitochondrial localization and interaction with ATP5A1 highlight its role in OXPHOS-mediated ATP production. The Prune1 inhibitor (LEO-AA7.5(S)T) was shown to impair tumor metastasis, enhance cell adhesion, and inhibit metabolic reprogramming by activating GSK-3 and NDPK-A. These findings underscore Prune1 as a potential therapeutic target for high-risk metastatic TNBC and cancers with altered glycolysis and OXPHOS pathways."],"dc:identifier":["https://hdl.handle.net/2434/1151635"],"dc:language":["eng"],"dc:publisher":["Università degli Studi di Milano","place:Ceinge, biotecnologie avanzate"],"dc:relation":["numberofpages:119"],"dc:rights":["info:eu-repo/semantics/embargoedAccess"],"dc:subject":["Settore MEDS-09/A - Oncologia medica"],"dc:title":["PRUNE_1 INVOLMENT IN TNBC ENHANCING CANCER METABOLISM"],"dc:type":["info:eu-repo/semantics/doctoralThesis"]},"updated_at":"2026-07-27T20:19:00Z"}