Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis.

ABSTRACT: 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^hiCD44^lo/- subpopulation as the SCLC metastasizing cell (SMC), which is progressively transitioned from the non-metastasizing NCAM^loCD44^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 kn

SUBMITTER: Jin Y 

PROVIDER: S-EPMC9365451 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature