Palbociclib sensitizes ER-positive breast cancer cells to fulvestrant by promoting the ubiquitin-mediated degradation of ER-α via SNHG17/Hippo-YAP axis

• DOI: 10.1007/s10549-023-07138-0
• Publication Date: 2023-11-04T14:01:46Z
• Authors: Lei Lei; Yuan Huang; Lei Shi; Weiwu Ye; Xianmei Lv; Lisha Ying; Xingfei Yu; Skye Hung-Chun Cheng; Yabing Zheng
• Keywords: Fulvestrant; Palbociclib

Abstract Purpose Endocrine therapy is the anti-tumor for human breast cancer but endocrine resistance was a major burden. It has been reported that Palbociclib and fulvestrant can be used in combination treatment of patients who are experiencing resistance. However, underlying mechanism unclear. In this study, we aimed to investigate by which Palbocicilib affected ER-positive cancer, combined with fulvestrant. Methods We first detected effect palbociclib on cell survival, growth cycle distribution separately MTT, colony formation flow cytometry. Then SNHG17 screened as palbociclib-targeted LncRNA LncRNA-seq, SNHG17-targeted mRNAs were selected mRNA-seq further determination. Subsequently, promoted cytotoxicity confirmed qRT-PCR, western blot, immunoprecipitation. Eventually, xenograft model immunohistochemistry experiments validate sensitization its vivo. Results significantly enhanced fulvestrant-resistant lines. Interestingly, might related lncRNA Hippo signaling pathway. And our subsequent blotting overexpressing induced down-regulation LATS1 up-regulated YAP expression. Furthermore, found increased sensitivity cells closely associated LATS1-mediated degradation ER-α. The following animal also indicated obviously impaired anti-cancer co-treatment accompanied decreased ER-α levels. Conclusion sensitize down-regulating expression, then resulted LATS1-inactivated oncogene