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    Cooperative behaviour and phenotype plasticity evolve during melanoma progression

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    Authors
    Rowling, E
    Miskolczi, Z
    Nagaraju, R
    Wilcock, DJ
    Wang, P
    Telfer, B
    Li, Y
    Lasheras-Otero, I
    Redondo-Munoz, M
    Sharrocks, AD
    Arozarena, I
    Wellbrock, Claudia
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    Affiliation
    Manchester Cancer Research Centre, Division of Cancer Sciences, United Kingdom
    Issue Date
    2020
    
    Metadata
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    Abstract
    A major challenge for managing melanoma is its tumour heterogeneity based on individual co-existing melanoma cell phenotypes. These phenotypes display variable responses to standard therapies, and they drive individual steps of melanoma progression; hence, understanding their behaviour is imperative. Melanoma phenotypes are defined by distinct transcriptional states, which relate to different melanocyte lineage development phases, ranging from a mesenchymal, neural crest-like to a proliferative, melanocytic phenotype. It is thought that adaptive phenotype plasticity based on transcriptional reprogramming drives melanoma progression, but at which stage individual phenotypes dominate and moreover, how they interact is poorly understood. We monitored melanocytic and mesenchymal phenotypes throughout melanoma progression and detected transcriptional reprogramming at different stages, with a gain in mesenchymal traits in circulating melanoma cells (CTCs) and proliferative features in metastatic tumours. Intriguingly, we found that distinct phenotype populations interact in a cooperative manner, which generates tumours of greater "fitness," supports CTCs and expands organotropic cues in metastases. Fibronectin, expressed in mesenchymal cells, acts as key player in cooperativity and promotes survival of melanocytic cells. Our data reveal an important role for inter-phenotype communications at various stages of disease progression, suggesting these communications could act as therapeutic target.
    Citation
    Rowling EJ, Miskolczi Z, Nagaraju R, Wilcock DJ, Wang P, Telfer B, et al. Cooperative behaviour and phenotype plasticity evolve during melanoma progression. Pigment Cell Melanoma Res. 2020.
    Journal
    Pigment Cell and Melanoma Research
    URI
    http://hdl.handle.net/10541/622877
    DOI
    10.1111/pcmr.12873
    PubMed ID
    32145051
    Additional Links
    https://dx.doi.org/10.1111/pcmr.12873
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1111/pcmr.12873
    Scopus Count
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    All Paterson Institute for Cancer Research

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