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However, the exact cell type contributing to metastasis remains elusive. Using a Rb1L\/L\/Trp53L\/L mouse model, we identify the NCAMhiCD44lo\/\u2013 subpopulation as the SCLC metastasizing cell (SMC), which is progressively transitioned from the non-metastasizing NCAMloCD44hi 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.<\/jats:p>","DOI":"10.1093\/nsr\/nwab232","type":"journal-article","created":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T07:14:03Z","timestamp":1640934843000},"source":"Crossref","is-referenced-by-count":22,"title":["Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis"],"prefix":"10.1093","volume":"9","author":[{"given":"Yujuan","family":"Jin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cell Biology, Chinese Academy of Sciences , Shanghai 200031 , China"},{"name":"Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences , Shanghai 200031 , China"},{"name":"Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences , Shanghai 200031 , 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