Cooperative behaviour and phenotype plasticity evolve during melanoma progression
AffiliationManchester Cancer Research Centre, Division of Cancer Sciences, United Kingdom
MetadataShow full item record
AbstractA 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.
CitationRowling 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.
JournalPigment Cell and Melanoma Research
- Phenotype plasticity as enabler of melanoma progression and therapy resistance.
- Authors: Arozarena I, Wellbrock C
- Issue date: 2019 Jul
- Melanoma Progression Inhibits Pluripotency and Differentiation of Melanoma-Derived iPSCs Produces Cells with Neural-like Mixed Dysplastic Phenotype.
- Authors: Castro-Pérez E, Rodríguez CI, Mikheil D, Siddique S, McCarthy A, Newton MA, Setaluri V
- Issue date: 2019 Jul 9
- Lineage-Restricted Regulation of SCD and Fatty Acid Saturation by MITF Controls Melanoma Phenotypic Plasticity.
- Authors: Vivas-García Y, Falletta P, Liebing J, Louphrasitthiphol P, Feng Y, Chauhan J, Scott DA, Glodde N, Chocarro-Calvo A, Bonham S, Osterman AL, Fischer R, Ronai Z, García-Jiménez C, Hölzel M, Goding CR
- Issue date: 2020 Jan 2
- The initial steps of tumor progression in melanocytic lineage: a histochemical approach.
- Authors: Wollina U, Kilian U, Henkel U, Schaarschmidt H, Knopf B
- Issue date: 1991 Jul-Aug
- Translation reprogramming is an evolutionarily conserved driver of phenotypic plasticity and therapeutic resistance in melanoma.
- Authors: Falletta P, Sanchez-Del-Campo L, Chauhan J, Effern M, Kenyon A, Kershaw CJ, Siddaway R, Lisle R, Freter R, Daniels MJ, Lu X, Tüting T, Middleton M, Buffa FM, Willis AE, Pavitt G, Ronai ZA, Sauka-Spengler T, Hölzel M, Goding CR
- Issue date: 2017 Jan 1