Equivocal, explicit and emergent actions of PKC isoforms in cancer
- 1 January 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Cancer
- Vol. 21 (1), 51-63
- https://doi.org/10.1038/s41568-020-00310-4
Abstract
The maturing mutational landscape of cancer genomes, the development and application of clinical interventions and evolving insights into tumour-associated functions reveal unexpected features of the protein kinase C (PKC) family of serine/threonine protein kinases. These advances include recent work showing gain or loss-of-function mutations relating to driver or bystander roles, how conformational constraints and plasticity impact this class of proteins and how emergent cancer-associated properties may offer opportunities for intervention. The profound impact of the tumour microenvironment, reflected in the efficacy of immune checkpoint interventions, further prompts to incorporate PKC family actions and interventions in this ecosystem, informed by insights into the control of stromal and immune cell functions. Drugging PKC isoforms has offered much promise, but when and how is not obvious. This Review discusses protein kinase C (PKC) isoforms in cancer, in particular focusing on their functional properties in the context of tumour suppression or promotion, target validation, PKC pharmacology and therapeutic exploitation.This publication has 154 references indexed in Scilit:
- Mitotic lamin disassembly is triggered by lipid-mediated signalingThe Journal of cell biology, 2012
- Regulation of Protein Kinase C-related Protein Kinase 2 (PRK2) by an Intermolecular PRK2-PRK2 Interaction Mediated by Its N-terminal DomainOnline Journal of Public Health Informatics, 2012
- Peptidyl-prolyl Isomerase Pin1 Controls Down-regulation of Conventional Protein Kinase C IsozymesJournal of Biological Chemistry, 2012
- The Phospholipase C Isozymes and Their RegulationSub-cellular biochemistry, 2012
- Active Site Inhibitors Protect Protein Kinase C from Dephosphorylation and Stabilize Its Mature FormOnline Journal of Public Health Informatics, 2011
- aPKCλ/ι promotes growth of prostate cancer cells in an autocrine manner through transcriptional activation of interleukin-6Proceedings of the National Academy of Sciences of the United States of America, 2009
- Spatiotemporal dynamics of lipid signaling: Protein kinase C as a paradigmIUBMB Life, 2008
- Targeting the protein kinase C family: are we there yet?Nature Reviews Cancer, 2007
- Mutations of the BRAF gene in human cancerNature, 2002
- Protein kinase Cδ controls self-antigen-induced B-cell toleranceNature, 2002