Fig. 4: G3BP1 deregulates potential oncogenic pathways and activates AR-mediated signaling.
From: G3BP1 inhibits Cul3SPOP to amplify AR signaling and promote prostate cancer
a, b Enriched signaling pathways of upregulated genes (a) and downregulated genes (b) after G3BP1 knockout (KO) by Gene Ontology analysis. c GSEA analysis of G3BP1 transcriptional signature from current study and TCGA cohort. d Distinct enriched oncogenic signatures between G3BP1 KO and siSPOP samples compared to normal samples via GSEA. e, f 22Rv1-sgCtrl and 22Rv1-sgG3BP1 cells were transfected with non-targeted or SPOP siRNA and designated as sgCtrl, siSPOP, sgG3BP1, and sgG3BP1 + siSPOP. e Inverse correlation and complementation of AR score39 in distinct genotypes. n = 3 biologically independent samples. In box plots, the center line represents median value, box limits represent 25% and 75% quantiles, and the top and bottom lines represent minimal and maximal values, respectively. f RT-qPCR for AR target genes, TMPRSS2, PSA, and KLK2 as indicated. Error bars ±S.E.M Paired t-test. g G3BP1 mRNA levels showed a stepwise upregulation with increasing AR output scores in different PCa cohort patients [TCGA, Provisional 201977; Taylor et al.64; SU2C, Robinson et al.15]. Unpaired t-test. p values are indicated in figure. In box plots, the center line represents median value, box limits represent 25% and 75% quantiles, and the top and bottom lines represent minimal and maximal values, respectively. h DOX-inducible empty vector (Ctrl) and pCW57.1-FLAG-G3BP1 (overexpressed) stable lines were generated from wild-type mPECs. n = 28 (Ctrl) and n = 52 (G3BP1 overexpressed) organoids examined over three independent experiments. Paired t-test (i) DOX-inducible empty vector (Ctrl) and pCW57.1-FLAG-G3BP1 (overexpressed) stable lines were generated from AR KO mPECs. n = 109 (Ctrl) and n = 109 (G3BP1 overexpressed) organoids examined over three independent experiments. Photomicrographs of representative mouse prostate organoids (scale bar, 200 µm) from the indicated mouse genotype following quantification of organoids (number and size). Unpaired t-test, Data are average of three independent experiments. Error bars, ±S.E.M. Source data are provided as a Source Data file.
