Lamin B1 loss promotes lung cancer development and metastasis by epigenetic derepression of RET
© 2019 Jia et al..
Although abnormal nuclear structure is an important criterion for cancer diagnostics, remarkably little is known about its relationship to tumor development. Here we report that loss of lamin B1, a determinant of nuclear architecture, plays a key role in lung cancer. We found that lamin B1 levels were reduced in lung cancer patients. Lamin B1 silencing in lung epithelial cells promoted epithelial-mesenchymal transition, cell migration, tumor growth, and metastasis. Mechanistically, we show that lamin B1 recruits the polycomb repressive complex 2 (PRC2) to alter the H3K27me3 landscape and repress genes involved in cell migration and signaling. In particular, epigenetic derepression of the RET proto-oncogene by loss of PRC2 recruitment, and activation of the RET/p38 signaling axis, play a crucial role in mediating the malignant phenotype upon lamin B1 disruption. Importantly, loss of a single lamin B1 allele induced spontaneous lung tumor formation and RET activation. Thus, lamin B1 acts as a tumor suppressor in lung cancer, linking aberrant nuclear structure and epigenetic patterning with malignancy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:216 |
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| Enthalten in: |
The Journal of experimental medicine - 216(2019), 6 vom: 03. Juni, Seite 1377-1395 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jia, Yanhan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.04.2020 Date Revised 13.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1084/jem.20181394 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM296355054 |
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| 245 | 1 | 0 | |a Lamin B1 loss promotes lung cancer development and metastasis by epigenetic derepression of RET |
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| 520 | |a © 2019 Jia et al. | ||
| 520 | |a Although abnormal nuclear structure is an important criterion for cancer diagnostics, remarkably little is known about its relationship to tumor development. Here we report that loss of lamin B1, a determinant of nuclear architecture, plays a key role in lung cancer. We found that lamin B1 levels were reduced in lung cancer patients. Lamin B1 silencing in lung epithelial cells promoted epithelial-mesenchymal transition, cell migration, tumor growth, and metastasis. Mechanistically, we show that lamin B1 recruits the polycomb repressive complex 2 (PRC2) to alter the H3K27me3 landscape and repress genes involved in cell migration and signaling. In particular, epigenetic derepression of the RET proto-oncogene by loss of PRC2 recruitment, and activation of the RET/p38 signaling axis, play a crucial role in mediating the malignant phenotype upon lamin B1 disruption. Importantly, loss of a single lamin B1 allele induced spontaneous lung tumor formation and RET activation. Thus, lamin B1 acts as a tumor suppressor in lung cancer, linking aberrant nuclear structure and epigenetic patterning with malignancy | ||
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| 700 | 1 | |a Asafova, Alina |e verfasserin |4 aut | |
| 700 | 1 | |a Garvalov, Boyan K |e verfasserin |4 aut | |
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| 700 | 1 | |a Singh, Anshu |e verfasserin |4 aut | |
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| 700 | 1 | |a Seeger, Werner |e verfasserin |4 aut | |
| 700 | 1 | |a Braun, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Savai, Rajkumar |e verfasserin |4 aut | |
| 700 | 1 | |a Dobreva, Gergana |e verfasserin |4 aut | |
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