| First Author | Jia Y | Year | 2019 |
| Journal | J Exp Med | Volume | 216 |
| Issue | 6 | Pages | 1377-1395 |
| PubMed ID | 31015297 | Mgi Jnum | J:276480 |
| Mgi Id | MGI:6314962 | Doi | 10.1084/jem.20181394 |
| Citation | Jia Y, et al. (2019) Lamin B1 loss promotes lung cancer development and metastasis by epigenetic derepression of RET. J Exp Med 216(6):1377-1395 |
| abstractText | 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. |
