Equivocal, explicit and emergent actions of PKC isoforms in cancer

Peter J. Parker; Sophie J. Brown; Veronique Calleja; Probir Chakravarty; Mathias Cobbaut; Mark Linch; Jacqueline J.T. Marshall; Silvia Martini; Neil Q. McDonald; Tanya Soliman; Lisa Watson

doi:10.1038/s41568-020-00310-4

Equivocal, explicit and emergent actions of PKC isoforms in cancer

Peter J. Parker^*, Sophie J. Brown, Veronique Calleja, Probir Chakravarty, Mathias Cobbaut, Mark Linch, Jacqueline J.T. Marshall, Silvia Martini, Neil Q. McDonald, Tanya Soliman, Lisa Watson

^*Corresponding author for this work

Comprehensive Cancer Centre

Research output: Contribution to journal › Review article › peer-review

39 Citations (Scopus)

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.

Original language	English
Pages (from-to)	51-63
Number of pages	13
Journal	NATURE REVIEWS CANCER
Volume	21
Issue number	1
DOIs	https://doi.org/10.1038/s41568-020-00310-4
Publication status	Published - Jan 2021

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title = "Equivocal, explicit and emergent actions of PKC isoforms in cancer",

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.",

author = "Parker, {Peter J.} and Brown, {Sophie J.} and Veronique Calleja and Probir Chakravarty and Mathias Cobbaut and Mark Linch and Marshall, {Jacqueline J.T.} and Silvia Martini and McDonald, {Neil Q.} and Tanya Soliman and Lisa Watson",

note = "Funding Information: The authors thank A. Fields and M. Reyland for commenting on the manuscript. They also acknowledge support from the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001130), the UK Medical Research Council (FC001130) and the Wellcome Trust (FC001130). M.L. is supported by the National Institute for Health Research, the University College London Hospitals Biomedical Research Centre (no grant numbers apply). Publisher Copyright: {\textcopyright} 2020, Springer Nature Limited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

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doi = "10.1038/s41568-020-00310-4",

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AU - Linch, Mark

AU - Marshall, Jacqueline J.T.

AU - Martini, Silvia

AU - McDonald, Neil Q.

AU - Soliman, Tanya

AU - Watson, Lisa

N1 - Funding Information: The authors thank A. Fields and M. Reyland for commenting on the manuscript. They also acknowledge support from the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001130), the UK Medical Research Council (FC001130) and the Wellcome Trust (FC001130). M.L. is supported by the National Institute for Health Research, the University College London Hospitals Biomedical Research Centre (no grant numbers apply). Publisher Copyright: © 2020, Springer Nature Limited. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

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N2 - 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.

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Equivocal, explicit and emergent actions of PKC isoforms in cancer

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