| First Author | Jin Y | Year | 2022 |
| Journal | Natl Sci Rev | Volume | 9 |
| Issue | 7 | Pages | nwab232 |
| PubMed ID | 35967587 | Mgi Jnum | J:345785 |
| Mgi Id | MGI:7610952 | Doi | 10.1093/nsr/nwab232 |
| Citation | Jin Y, et al. (2022) Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis. Natl Sci Rev 9(7):nwab232 |
| abstractText | Small-cell lung cancer (SCLC) is a recalcitrant cancer characterized by high metastasis. However, the exact cell type contributing to metastasis remains elusive. Using a Rb1 (L/L) /Trp53 (L/L) mouse model, we identify the NCAM(hi)CD44(lo/-) subpopulation as the SCLC metastasizing cell (SMC), which is progressively transitioned from the non-metastasizing NCAM(lo)CD44(hi) cell (non-SMC). Integrative chromatin accessibility and gene expression profiling studies reveal the important role of the SWI/SNF complex, and knockout of its central component, Brg1, significantly inhibits such phenotypic transition and metastasis. Mechanistically, TAZ is silenced by the SWI/SNF complex during SCLC malignant progression, and its knockdown promotes SMC transition and metastasis. Importantly, ectopic TAZ expression reversely drives SMC-to-non-SMC transition and alleviates metastasis. Single-cell RNA-sequencing analyses identify SMC as the dominant subpopulation in human SCLC metastasis, and immunostaining data show a positive correlation between TAZ and patient prognosis. These data uncover high SCLC plasticity and identify TAZ as the key molecular switch in orchestrating SCLC phenotypic transition and metastasis. |
