Supplementary Materials

Supplementary Materials for:

Targeting aPKC disables oncogenic signaling by both the EGFR and the proinflammatory cytokine TNFα in glioblastoma

Yael Kusne, Eugenio A. Carrera-Silva, Anthony S. Perry, Elisabeth J. Rushing, Edward K. Mandell, Justin D. Dietrich, Andrea E. Errasti, Daniel Gibbs, Michael E. Berens, Joseph C. Loftus, Christopher Hulme, Weiwei Yang, Zhimin Lu, Kenneth Aldape, Nader Sanai, Carla V. Rothlin,* Sourav Ghosh*

*Corresponding author. E-mail: carla.rothlin@yale.edu (C.V.R.); sourav.ghosh@yale.edu (S.G.)

This PDF file includes:

  • Fig. S1. aPKC immunostaining in nontumor brain and in histologically characteristic regions of glioblastoma.
  • Fig. S2. Validation of aPKC knockdown efficiencies and the inhibitory effect of PZ09.
  • Fig. S3. EGFR isoform abundance in GBM6 and EGFR phosphorylation kinetics in GBM6 and U251/EGFR cells.
  • Fig. S4. Myeloid cells, TNFα production, and NF-κB activation in mouse models of glioblastoma.
  • Fig. S5. Expression and sequence of NFKB1A in two independent glioblastoma specimens.
  • Fig. S6. Myeloid cells produce TNFα when cocultured with glioblastoma cells.
  • Fig. S7. Coculture with monocytes increases GBM6 cell invasion.
  • Fig. S8. Human myeloid cell–derived TNFα contributes to increased proliferation and invasion of GBM6 cells.
  • Fig. S9. Murine myeloid cell–derived TNFα contributes to increased glioblastoma proliferation and invasion.
  • Fig. S10. TNFα-induced NF-κB signaling in U251/EGFR cells depends on aPKC.
  • Fig. S11. Phosphorylation of aPKC precedes phosphorylation of p65.
  • Fig. S12. Activation of aPKC and induction of NF-κB–dependent genes in glioblastoma cells upon coculture with myeloid cells.
  • Fig. S13. Myeloid cell–mediated induction of proliferation and invasion of glioblastoma cells depends on aPKC.
  • Fig. S14. aPKC inhibition does not suppress the phosphorylation of EGFR.
  • Fig. S15. Induction of distinct sets of genes by EGF and TNFα signaling in glioblastoma cells.
  • Fig. S16. Validation of EGFR, AKT, and Src inhibition in U87/EGFRvIII cells.
  • Fig. S17. PRKCI is the predominant aPKC isoform that shows increased abundance in glioblastoma.
  • Table S1. List of primers.
  • Table S2. List of siRNA and shRNA sequences.

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Citation: Y. Kusne, E. A. Carrera-Silva, A. S. Perry, E. J. Rushing, E. K. Mandell, J. D. Dietrich, A. E. Errasti, D. Gibbs, M. E. Berens, J. C. Loftus, C. Hulme, W. Yang, Z. Lu, K. Aldape, N. Sanai, C. V. Rothlin, S. Ghosh, Targeting aPKC disables oncogenic signaling by both the EGFR and the proinflammatory cytokine TNFα in glioblastoma. Sci. Signal. 7, ra75 (2014).

© 2014 American Association for the Advancement of Science