The isomerase PIN1 controls numerous cancer-driving pathways and is a unique drug target

Targeted drugs have changed cancer treatment but are often ineffective in the long term against solid tumours, largely because of the activation of heterogeneous oncogenic pathways. A central common signalling mechanism in many of these pathways is proline-directed phosphorylation, which is regulate...

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Published inNature reviews. Cancer Vol. 16; no. 7; pp. 463 - 478
Main Authors Zhou, Xiao Zhen, Lu, Kun Ping
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.07.2016
Subjects
Animals
Carcinogenesis
Cellular control mechanisms
Genetic aspects
Health aspects
Humans
Innovations
Isomerases
Isomerism
Mice
Molecular targeted therapy
Neoplasms - drug therapy
Neoplasms - enzymology
NIMA-Interacting Peptidylprolyl Isomerase - drug effects
NIMA-Interacting Peptidylprolyl Isomerase - physiology
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Summary:Targeted drugs have changed cancer treatment but are often ineffective in the long term against solid tumours, largely because of the activation of heterogeneous oncogenic pathways. A central common signalling mechanism in many of these pathways is proline-directed phosphorylation, which is regulated by many kinases and phosphatases. The structure and function of these phosphorylated proteins are further controlled by a single proline isomerase: PIN1. PIN1 is overactivated in cancers and it promotes cancer and cancer stem cells by disrupting the balance of oncogenes and tumour suppressors. This Review discusses the roles of PIN1 in cancer and the potential of PIN1 inhibitors to restore this balance.
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ISSN:1474-175X
1474-1768
DOI:10.1038/nrc.2016.49