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. 2017 Aug 1;4(7-8):79–94. doi: 10.18632/oncoscience.356

Figure 3. TAZ-TEAD1 activation in LP-1/Cfz cells confers resistance to carfilzomib.

Figure 3

A. TAZ levels are increased in LP-1/Cfz (Cfz) versus parental LP-1 cells (1.6 ± 0.3-fold, n = 10, P < 0.01). Cells were pretreated with MG-132 (15 μM) for 18 hours to prevent proteasomal degradation. B. TEAD1 levels are increased in LP-1/Cfz (Cfz) versus parental LP-1 cells (2.2 ± 0.3-fold, n = 10, P < 0.01). Cells were pretreated with MG-132 (15 μM) for 18 hours to prevent proteasomal degradation. C. siRNA-mediated knockdown of TAZ slightly sensitized LP-1/Cfz cells to carfilzomib. Consistent with low YAP1 levels in LP-1/Cfz cells, siRNA-mediated knockdown of YAP1 in concert with TAZ did not meaningfully enhance sensitization of the cells to the drug. LP-1/Cfz cells were significantly sensitized to carfilzomib by combined siRNA-mediated knockdown of TAZ and TEAD1. No effects were observed on parental LP-1 cells under any of the conditions. Cells were treated with carfilzomib (12.5 nM) for 48 hours after transient transfection and cell viability was determined by alamarBlue assay. *, P = 0.04 vs negative siRNA control (siNeg, n = 3). D, E. siRNA-mediated knockdown of TAZ and TEAD1 in LP-1/Cfz cells was accompanied by decreased TAZ (40 ± 15% decrease) (D) and TEAD1 (57 ± 6% decrease) (E) levels.