GSE161740
YAP governs intratumoral heterogeneity and chemosensitivity of small cell lung cancer [bulk RNA-seq]
Small cell lung cancer is the most aggressive type of lung cancer and has a high degree of plasticity, characterized by a remarkable response to chemotherapy followed by development of resistance. We show that intratumoral heterogeneity of SCLC is progressively established, indicated by the appearance of YAP+ and HES1+ SCLC tumor cells. Notch signaling is required for the generation of Non-NE SCLC cells, but not for the tumorigenesis of SCLC. Furthermore, YAP signals through Notch-dependent and independent pathway to induce REST expression to promote the conversion of NE to Non-NE SCLC tumor cells. In addition, YAP activation enhances the chemoresistance in NE SCLC tumor cells by downregulating GSDME, while inactivation of YAP in Non-NE SCLC tumor cells switches cell death from apoptosis to pyroptosis. Our study will not only provide novel insights into the molecular basis of SCLC tumorigenesis, but also the potential drug targets for SCLC therapy Overall design: RNA-seq comparing NE, Non-NE and OE-YAP5SA NE mSCLC cell lines