Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation
© 2024. The Author(s)..
Hyperthermic intraperitoneal chemotherapy's role in ovarian cancer remains controversial, hindered by limited understanding of hyperthermia-induced tumor cellular changes. This limits developing potent combinatory strategies anchored in hyperthermic intraperitoneal therapy (HIPET). Here, we perform a comprehensive multi-omics study on ovarian cancer cells under hyperthermia, unveiling a distinct molecular panorama, primarily characterized by rapid protein phosphorylation changes. Based on the phospho-signature, we pinpoint CDK1 kinase is hyperactivated during hyperthermia, influencing the global signaling landscape. We observe dynamic, reversible CDK1 activity, causing replication arrest and early mitotic entry post-hyperthermia. Subsequent drug screening shows WEE1 inhibition synergistically destroys cancer cells with hyperthermia. An in-house developed miniaturized device confirms hyperthermia and WEE1 inhibitor combination significantly reduces tumors in vivo. These findings offer additional insights into HIPET, detailing molecular mechanisms of hyperthermia and identifying precise drug combinations for targeted treatment. This research propels the concept of precise hyperthermic intraperitoneal therapy, highlighting its potential against ovarian cancer.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 07. März, Seite 2089 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Xiaohang [VerfasserIn] |
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| Links: |
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| Themen: |
CDC2 Protein Kinase |
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| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 11.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-024-46358-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369437047 |
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| 520 | |a Hyperthermic intraperitoneal chemotherapy's role in ovarian cancer remains controversial, hindered by limited understanding of hyperthermia-induced tumor cellular changes. This limits developing potent combinatory strategies anchored in hyperthermic intraperitoneal therapy (HIPET). Here, we perform a comprehensive multi-omics study on ovarian cancer cells under hyperthermia, unveiling a distinct molecular panorama, primarily characterized by rapid protein phosphorylation changes. Based on the phospho-signature, we pinpoint CDK1 kinase is hyperactivated during hyperthermia, influencing the global signaling landscape. We observe dynamic, reversible CDK1 activity, causing replication arrest and early mitotic entry post-hyperthermia. Subsequent drug screening shows WEE1 inhibition synergistically destroys cancer cells with hyperthermia. An in-house developed miniaturized device confirms hyperthermia and WEE1 inhibitor combination significantly reduces tumors in vivo. These findings offer additional insights into HIPET, detailing molecular mechanisms of hyperthermia and identifying precise drug combinations for targeted treatment. This research propels the concept of precise hyperthermic intraperitoneal therapy, highlighting its potential against ovarian cancer | ||
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| 700 | 1 | |a Li, Wenting |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Junpeng |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Funian |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Tianyu |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Xiaoyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuang, Xucui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Fuxia |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Rourou |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Tingyan |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Kun |e verfasserin |4 aut | |
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| 700 | 1 | |a Chen, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Chaoyang |e verfasserin |4 aut | |
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