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. Author manuscript; available in PMC: 2022 Apr 5.
Published in final edited form as: Cancer Cell. 2021 Jul 21;39(8):1115–1134.e12. doi: 10.1016/j.ccell.2021.06.016

Figure 2. Obligate YAP/TAZ silencing in SCLC.

Figure 2.

(A) Western blots of SCLC, NSCLC cell lines.

(B) YAP/TAZ and p16 (marker for RB1 loss) IHC in primary human SCLC and NSCLC PDXs (left) and scoring (right). Scale bars, 300 µm.

(C) YAP and TAZ mRNA in primary human lung tumors. *p < 0.05, **p < 0.01, ***p < 0.001, *****p < 1 × 10–5.

(D) Western blots of YAP/TAZ in SCLC and NSCLC PDXs. PDXs are from different donors, except the paired treatment naive (N) and cisplatin/etoposide-resistant (R) LX108 samples.

(E) Violin plot of low Yap and Taz mRNA in murine SCLC.

(F) Yap/Taz IF in CgrpCreER;Rb1f/f;p53f/f SCLC. Neighboring airway/alveolar cells express Yap/Taz but not dividing Syp+ NE cells. Note rare Syp–;Ki67–;Yap/Taz+ cells within tumor. Scale bar, 20 µm.

(G) IHC for Ccsp-rtTA;tetO-EGFRL858R NSCLC and Ad-CMV-Cre-Rb1f/f;p53f/f;Ptenf/+ SCLC. Scale bar, 100 µm.

(H) IF on embryonic day 18.5 (E18.5) Spc-rtTA;tetO-Cre;Rb1f/f;p53f/f lungs. Orange arrows, Yap– dividing (Ki67+) NE cells (Syp+); white arrows, Yap+ dividing non-NE cells (Syp–). Scale bar, 20 µm.

(I) Ectopic YAP or hyperactive YAP5SA (n = 3, p < 0.05) but not YAPS94A impede growth of SCLC lines.

(J) Ectopic TAZ suppresses growth of SCLC lines (n = 3, p < 0.0001).

(K) Outline for murine SCLC +/– Yap (left), images (middle), and area (right) of control and Yap+ SCLC 3 months after tam/dox. NEB, NE bundle. t test with Welch’s correction. Scale bars, 50 µm.

(L) Graphs show number (left) and size (middle) of dividing NEB in Rb1f/f;p53f/f or Rb1f/f;p53f/f;Yapf/f;Tazf/f mice 2 or 3 months after Ad-CMV-Cre administration. Mean ± SD, n = 3 (3 months) or 4 (2 months) mice/genotype; *p < 0.05, **p < 0.01. Representative images (right) are from 3 month mice. Scale bars, 200 µm. See also Figure S2.