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    Cdc6 as a novel target in cancer: oncogenic potential, senescence and subcellular localisation

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    Authors
    Lim, N
    Townsend, Paul A
    Affiliation
    Division of Cancer Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, Manchester Cancer Research Centre, NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester, UK
    Issue Date
    2020
    
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    Abstract
    Cdc6 is a key replication licencing factor with a pivotal role in regulating the process of DNA replication, rendering it an important investigatory focus in tumourigenesis. Indeed, Cdc6 overexpression has been found to be a feature in certain tumours and has been associated as an early event in malignancies. With a focus on pancreatic cancer, there are evidence of its convergence in downstream pathways implicated in major genetic alterations found in pancreatic cancer, primarily KRAS. There is also data of its direct influence on protumourigenic processes as a transcriptional regulator, repressing the key tumour suppressor loci CDH1 (E-Cadherin) and influencing epithelial to mesenchymal transition (EMT). Moreover, gene amplification of Cdc6 as well as of E2F (an upstream regulator of Cdc6) have also been found to be a key feature in tumours overexpressing Cdc6, further highlighting this event as a potential driver of tumourigenesis. In this review, we summarise the evidence for the role of Cdc6 overexpression in cancer, specifically that of pancreatic cancer. More importantly, we recapitulate the role of Cdc6 as part of the DNA damage response and on senescence-an important antitumour barrier-in the context of pancreatic cancer. Finally, recent emerging observations suggest that the potential of the subcellular localisation of Cdc6 in inducing senescence. In this regard, we speculate and hypothesise potentially exploitable mechanisms in the context of inducing senescence via a novel pathway involving cytoplasmic retention of Cdc6 and Cyclin E.
    Citation
    Lim N, Townsend PA. Cdc6 as a novel target in cancer: Oncogenic potential, senescence and subcellular localisation. Int J Cancer. 2020.
    Journal
    International Journal of Cancer
    URI
    http://hdl.handle.net/10541/622780
    DOI
    10.1002/ijc.32900
    PubMed ID
    32010971
    Additional Links
    https://dx.doi.org/10.1002/ijc.32900
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1002/ijc.32900
    Scopus Count
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    All Paterson Institute for Cancer Research

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