Fig. 1: Casein kinase II is a novel regulator of YAP1 turnover in multiple types of cancers.

A Strategy used to identify small molecule compounds mitigating GFP-YAP1 stability. B Among screening hits with in-house small molecule compounds library, the specific inhibitor of Casein kinase II, Silmitasertib, caused the highest inhibitory effect on YAP1. C A2780 and SKOV3 cells were treated with Silmitasertib at different concentrations, and the protein level of YAP1 was measured by immunobloting. D A2780 and SKOV3 cells were treated with DMSO or Silmitasertib. mRNA levels of YAP1 target genes CTGF, CYR61 and ANKRD1 were measured by qRT-PCR (n = 3), standardized to GAPDH and normalized. E Vector (V) or Flag-YAP1 were transfected into A2780 cells and then treated with DMSO or Silmitasertib. The protein level of YAP1 was measured by immunoblotting. F The proliferation of cells used in (E) was measured and analyzed. G Indicated concentrations of Cisplatin were treated into cells used in (E), and a CCK8 assay was performed to measure cell survival. H Vector (V) or Flag-YAP1 were transfected in Control (Ctrl) or CK2α-depleted A2780 cells, and the protein level of YAP1 was measured by immunoblotting. I The proliferation of cells used in (H) was measured and analyzed. J Indicated concentrations of Cisplatin were treated into cells used in (H), and a CCK8 assay was performed to measure cell survival. K and L Cells generated in (E) were implanted subcutaneously into nude mice (n = 6). When tumors grew to around 100–150 mm³, mice were randomly grouped and administered with saline, Silmitasertib (60 mg/kg, p.o. twice per day), cisplatin (5 mg/kg i.p. every 3 days), or a combination of Silmitasertib and cisplatin. Tumors were collected (K) and tumor weights were analyzed (L). M Silmitasertib was treated in H460, A549, PANC-1, MIAPaCa-2, MDA-MB-231, 786-O, RCC4, Huh-7, HCT-116 and LoVo cells for 24 h. The protein level of YAP1 was measured by immunoblotting. N MIAPaCa-2, PANC-1, MDA-MB-231, H460, 786-O and LoVo cells with the depletion of CK2α were generated. YAP1 and CK2α protein levels were measured by immunoblotting.