Mp16-05 lowering Mrna Expression of Plekho1 Inhibits Tumor Growth of RCC Cells in Vitro and in Vivo, Potentially Through Modulating the Hippo and Mapk/JNK Signalling Pathways

Abstract

estrogens, shRNA knockdown of ERb and ectopic expression of ERb could affect RCC cell proliferation, migration and invasion. TCGA database analysis showed that the increased ERb is associated with a worse survival for RCC patients. Mechanism analysis revealed that ERb can promote RCC cell invasion via increasing transforming growth factor b1 (TGF-b1)/SMAD3 signals, and interrupting TGF-b 1/SMAD3 signals with a TGFb R1 inhibitor can reverse/block ERb -increased RCC cell migration.CONCLUSIONS: ERb can promote RCC cell invasion via upregulating TGF-b1)/SMAD3 signals. Compared to Faslodex and PHTPP, tamoxifen is not an effective anti-estrogen for RCC treatment. Importantly, preclinical analyses using in vivo mouse models of RCC revealed that targeting of this newly identified ERb/TGF-b1/SMAD3 pathway with either the FDA-approved antiestrogen ICI182,780 (Faslodex) or a selective ERb antagonist PHTPP can significantly reduce RCC tumor growth and invasion, which may be suitable as the basis for novel therapies to more effectively suppress metastatic RCC.