Cellular Reprogramming—A Model for Melanoma Cellular Plasticity

Granados, Karol; Poelchen, Juliane; Novak, Daniel; Utikal, Jochen

doi:10.3390/ijms21218274

Cited by 17 publications

(15 citation statements)

References 94 publications

(142 reference statements)

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“…Extensive molecular characterization of the NZM lines has revealed that the panel closely matches the spectrum of molecular alterations observed in melanomas analyzed from patients in the general population [110]. An analysis of the invasiveness of NZM melanoma cell lines indicated that, as has been observed in other melanoma cell line panels [97,98,118,119], the NZM cell lines could be grouped into both invasive and non-invasive subgroups, with a characteristic gene expression signature corresponding to each subgroup [103,108]. Thus, for these two sub-groups of the NZM cell lines, the reported patterns of gene expression were similar to those of Hoek et al, 2008 [97,103,108].…”

Section: Transcriptomic Differences Between Invasive and Non-invasive Phenotypesmentioning

confidence: 53%

Genetic and Genomic Pathways of Melanoma Development, Invasion and Metastasis

Motwani

Eccles

2021

Genes

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Melanoma is a serious form of skin cancer that accounts for 80% of skin cancer deaths. Recent studies have suggested that melanoma invasiveness is attributed to phenotype switching, which is a reversible type of cell behaviour with similarities to epithelial to mesenchymal transition. Phenotype switching in melanoma is reported to be independent of genetic alterations, whereas changes in gene transcription, and epigenetic alterations have been associated with invasiveness in melanoma cell lines. Here, we review mutational, transcriptional, and epigenomic alterations that contribute to tumour heterogeneity in melanoma, and their potential to drive melanoma invasion and metastasis. We also discuss three models that are hypothesized to contribute towards aspects of tumour heterogeneity and tumour progression in melanoma, namely the clonal evolution model, the cancer stem cell model, and the phenotype switching model. We discuss the merits and disadvantages of each model in explaining tumour heterogeneity in melanoma, as a precursor to invasion and metastasis.

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Section: Transcriptomic Differences Between Invasive and Non-invasive Phenotypesmentioning

confidence: 53%

Genetic and Genomic Pathways of Melanoma Development, Invasion and Metastasis

Motwani

Eccles

2021

Genes

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“…The cellular plasticity of cancer cells and phenotypic heterogeneity remain a major challenge for the treatment of melanoma and other types of cancer 47 , 48 . In the present report, it is shown that melanoma cells have the capacity to switch their phenotype under treatment from a differentiated phenotype to a more de-differentiated phenotype.…”

Section: Discussionmentioning

confidence: 99%

Single-cell trajectories of melanoma cell resistance to targeted treatment

Schmidt¹,

Mortensen²,

Loeffler‐Wirth³

et al. 2021

Cancer Biol. Med.

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Objective: Cellular heterogeneity is regarded as a major factor affecting treatment response and resistance in malignant melanoma. Recent developments in single-cell sequencing technology have provided deeper insights into these mechanisms. Methods: Here, we analyzed a BRAF V600E -mutant melanoma cell line by single-cell RNA-seq under various conditions: cells sensitive to BRAF inhibition with BRAF inhibitor vemurafenib and cells resistant to BRAF inhibition with vemurafenib alone or vemurafenib in combination with the MEK1/2 inhibitors cobimetinib or trametinib. Dimensionality reduction by t-distributed stochastic neighbor embedding and self-organizing maps identified distinct trajectories of resistance development clearly separating the 4 treatment conditions in cell and gene state space. Results: Trajectories associated with resistance to single-agent treatment involved cell cycle, extracellular matrix, and de-differentiation programs. In contrast, shifts detected in double-resistant cells primarily affected translation and mitogen-activated protein kinase pathway reactivation, with a small subpopulation showing markers of pluripotency. These findings were validated in pseudotime analyses and RNA velocity measurements. Conclusions: The single-cell transcriptomic analyses reported here employed a spectrum of bioinformatics methods to identify mechanisms of melanoma resistance to single-and double-agent treatments. This study deepens our understanding of treatmentinduced cellular reprogramming and plasticity in melanoma cells and identifies targets of potential relevance to the management of treatment resistance.

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“…Another way to create apoptosis-resistant CSCs involves dedifferentiation and reprogramming. In particular, numerous lines of evidence have established that CSCs have the potential to transdifferentiate into other lineage cells (pericytes vascular and endothelial cells) for promoting tumor growth and metastasis in some tissue contexts instead of only recruiting stromal cells from neighboring or distant tissues [ 53 ].…”

Section: Apoptosismentioning

confidence: 99%

The Great Escape: The Power of Cancer Stem Cells to Evade Programmed Cell Death

Castelli

Giordano

Benedetti

et al. 2021

Cancers

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Cancer is one of the primary causes of death worldwide. Tumour malignancy is related to tumor heterogeneity, which has been suggested to be due to a small subpopulation of tumor cells named cancer stem cells (CSCs). CSCs exert a key role in metastasis development, tumor recurrence, and also epithelial–mesenchymal transition, apoptotic resistance, self-renewal, tumorigenesis, differentiation, and drug resistance. Several current therapies fail to eradicate tumors due to the ability of CSCs to escape different programmed cell deaths. Thus, developing CSC-selective and programmed death-inducing therapeutic approaches appears to be of primary importance. In this review, we discuss the main programmed cell death occurring in cancer and the promising CSC-targeting agents developed in recent years. Even if the reported studies are encouraging, further investigations are necessary to establish a combination of agents able to eradicate CSCs or inhibit their growth and proliferation.

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Cellular Reprogramming—A Model for Melanoma Cellular Plasticity

Cited by 17 publications

References 94 publications

Genetic and Genomic Pathways of Melanoma Development, Invasion and Metastasis

Genetic and Genomic Pathways of Melanoma Development, Invasion and Metastasis

Single-cell trajectories of melanoma cell resistance to targeted treatment

The Great Escape: The Power of Cancer Stem Cells to Evade Programmed Cell Death

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