Fig. 6: Entinostat inhibits SCLC metastasis. | Nature Communications

Fig. 6: Entinostat inhibits SCLC metastasis.

From: YAP silencing by RB1 mutation is essential for small-cell lung cancer metastasis

Fig. 6

a Entinostat (1 µM, 24 hours) inhibits H209 cell ameboid migration under confinement. b Entinostat decreases H209 cell F-actin intensity in vitro. The fluorescence image and quantification of Lifeact-TagGFP are shown in the left and right panel, respectively. c Entinostat inhibits liver metastasis of orthotopically grafted H209 cells. HE staining shows liver metastasis. Quantification of metastasis sites per mouse is shown in the right panel. d Entinostat treatment decreases F-actin intensity in H209 xenografted tumors. Quantification is shown in the right panel. e Entinostat reduces CTCs in mice orthotopically inoculated with EGFP-labeled H209 or H526 cells. EGFP-positive CTCs in blood were detected by flow cytometry. f Entinostat reduces CTCs in mice orthotopically inoculated with either H209 or H526 cells. Experiments were similar to d, except CTCs were quantified by human GAPDH mRNA normalized against mouse GAPDH mRNA. g Entinostat prolongs survival of H209 xenografted mice. Nude mice were orthotopically inoculated with 5 × 106 H209 cells. Seven days later, mice were orally treated with a control vehicle or 12.3 mg/kg entinostat once daily, five days per week, until the terminal event. h Entinostat acts through YAP to decrease H209 cell F-actin intensity in vitro. The fluorescence image and quantification of Lifeact-TagGFP are shown in the left and right panel, respectively. i Entinostat acts through YAP to inhibit H209 cell ameboid cell migration. j Entinostat acts through YAP to inhibit F-actin in the H209 orthotopic model. Quantification is shown in the right panel. k YAP KO blocks the inhibitory effect of entinostat on CTCs in H209 cells. l YAP is required for entinostat to inhibit H209 liver metastasis. Source data are provided as a Source data file.

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