Fig. 8: Targeting ERBB2 inhibits oncogenic effects of KLF5.
From: Opposing transcriptional programs of KLF5 and AR emerge during therapy for advanced prostate cancer
a Viability assays of patient-derived organoids developed from neuroendocrine CRPC (OWCM154 and 155) or CRPC adenocarcinoma (MSK-PCA3) treated with neratinib. Data are mean ±95% CI from three independent experiments in biological triplicate (n = 9). b, Lapatinib sensitivity scores predicted using ridge regression models trained on high-throughput cancer cell line drug screens in metastatic CRPC tumors (SU2C-EC study), plotted vs. KLF5 expression (FPKM = fragments per kb per million fragments mapped). Pearson correlation coefficients (R) and 2-tailed p-values for r ≠ 0 are shown. c Lapatinib sensitivity scores as in b plotted vs. KLF5 activity score. d–g 2-dimensional growth assays for R1-AD1 cells, R1-D567 cells, LNCaP cells infected with empty lentivirus (LNCaP-Vector), and LNCaP cells infected with lentivirus encoding KLF5 (LNCaP-KLF5) cultured in androgen-replete medium and treated for 5 days with mubritinib. Gray lines are biological replicates (n = 6), black lines are mean ±95% CI, IC50 values are mean ±95% CI. h, i LNCaP cells as in f and g were analyzed by 3D soft agar colony formation assays in androgen-replete medium supplemented with lapatinib or mubritinib. n = 4, mean ±95% CI, two independent experiments in biological duplicate. j LNCaP cells as in f and g analyzed by chemotactic migration assays with the medium in the top chamber containing 10 nM mubritinib or vehicle control (DMSO). n = 6, mean ±95% CI, two independent experiments in biological triplicate. P-values are from unpaired 2-sided t-tests.
