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Kenchappa RS, Liu Y, Argenziano MG, et al. Protein kinase C. Cell Rep. 2021;37(8):110054doi: 10.1016/j.celrep.2021.110054.
Kenchappa, R. S., Liu, Y., Argenziano, M. G., Banu, M. A., Mladek, A. C., West, R., Luu, A., Quiñones-Hinojosa, A., Hambardzumyan, D., Justilien, V., Leitges, M., Sarkaria, J. N., Sims, P. A., Canoll, P., Murray, N. R., Fields, A. P., & Rosenfeld, S. S. (2021). Protein kinase C. Cell reports, 37(8), 110054. https://doi.org/10.1016/j.celrep.2021.110054
Kenchappa, Rajappa S, et al. "Protein kinase C." Cell reports vol. 37,8 (2021): 110054. doi: https://doi.org/10.1016/j.celrep.2021.110054
Kenchappa RS, Liu Y, Argenziano MG, Banu MA, Mladek AC, West R, Luu A, Quiñones-Hinojosa A, Hambardzumyan D, Justilien V, Leitges M, Sarkaria JN, Sims PA, Canoll P, Murray NR, Fields AP, Rosenfeld SS. Protein kinase C. Cell Rep. 2021 Nov 23;37(8):110054. doi: 10.1016/j.celrep.2021.110054. PMID: 34818553.
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Cell Rep. 2021 Nov 23;37(8):110054. doi: 10.1016/j.celrep.2021.110054.

Protein kinase C.

Cell reports

Rajappa S Kenchappa, Yi Liu, Michael G Argenziano, Matei A Banu, Ann C Mladek, Rita West, Amanda Luu, Alfredo Quiñones-Hinojosa, Dolores Hambardzumyan, Verline Justilien, Michael Leitges, Jann N Sarkaria, Peter A Sims, Peter Canoll, Nicole R Murray, Alan P Fields, Steven S Rosenfeld

Affiliations

  1. Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA. Electronic address: [email protected].
  2. Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA.
  3. Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
  4. Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55902, USA.
  5. Department of Neurosurgery, Mayo Clinic, Jacksonville, FL 32224, USA.
  6. Departments of Neurosurgery and Oncological Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.
  7. Memorial University of Newfoundland, St. John's, NL, Canada.
  8. Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA.
  9. Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA. Electronic address: [email protected].
  10. Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA. Electronic address: [email protected].
  11. Department of Cancer Biology, Mayo Clinic, Jacksonville, FL 32224, USA. Electronic address: [email protected].

PMID: 34818553 DOI: 10.1016/j.celrep.2021.110054

Abstract

We report that atypical protein kinase Cι (PKCι) is an oncogenic driver of glioblastoma (GBM). Deletion or inhibition of PKCι significantly impairs tumor growth and prolongs survival in murine GBM models. GBM cells expressing elevated PKCι signaling are sensitive to PKCι inhibitors, whereas those expressing low PKCι signaling exhibit active SRC signaling and sensitivity to SRC inhibitors. Resistance to the PKCι inhibitor auranofin is associated with activated SRC signaling and response to a SRC inhibitor, whereas resistance to a SRC inhibitor is associated with activated PKCι signaling and sensitivity to auranofin. Interestingly, PKCι- and SRC-dependent cells often co-exist in individual GBM tumors, and treatment of GBM-bearing mice with combined auranofin and SRC inhibitor prolongs survival beyond either drug alone. Thus, we identify PKCι and SRC signaling as distinct therapeutic vulnerabilities that are directly translatable into an improved treatment for GBM.

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords: SRC; glioblastoma; kinase inhibitor; protein kinase C iota

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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