Figure 6.

Low TAZ level is correlated with SCN signature enrichment and predicts poor prognosis of SCLC patients. (A) Schematic illustration of the analyses of human SCLC specimens. (B) SCN score of human SCLC specimens with high or low TAZ mRNA level. The RNA-seq data were downloaded from a public database (GSE69091 and EGAS00001000334). Data are shown as mean ± S.E.M. P value was calculated by unpaired two-tailed t test. (C) Correlation between individual SCN-signature-related genes, CD44 or TEAD2 expression with high or low TAZ level in human SCLC (GSE69091 and EGAS00001000334). Data are shown as mean ± S.E.M. P values were calculated by unpaired two-tailed t test. (D) Clustering and the NCAM, CD44, TAZ, NEUROD1 and INSM1 expression of the single cell sequencing data (GSM4558305) of a liver biopsy from an SCLC patient. (E and F) Representative photos of (E) NCAM, CD44 and (F) TAZ IHC staining in Chinese SCLC specimens (top) and survival curves of high or low expression of NCAM, CD44 or TAZ with overall survival (OS) (bottom). Scale bar, 100 μm. P values were calculated by Kaplan-Meier analysis with log-rank test. (G) Working model illustrating the essential role of SWI/SNF-complex-mediated TAZ expression in controlling the phenotypic transition from non-SMC to SMC and SCLC metastasis. TAZ, which is epigenetically silenced by the SWI/SNF complex, functions as a critical molecular switch during the phenotypic transition from non-SMC to SMC and SCLC metastasis. Disruption of the SWI/SNF complex through BRG1 knockout promotes TAZ upregulation and thus inhibits the phenotypic transition and cancer metastasis.