Melanoma Progression Inhibits Pluripotency and Differentiation of Melanoma-Derived iPSCs Produces Cells with Neural-like Mixed Dysplastic Phenotype.

Melanoma Progression Inhibits Pluripotency and Differentiation of Melanoma-Derived iPSCs Produces Cells with Neural-like Mixed Dysplastic Phenotype.

Publication date: Jul 09, 2019

Melanomas are known to exhibit phenotypic plasticity. However, the role cellular plasticity plays in melanoma tumor progression and drug resistance is not fully understood. Here, we used reprogramming of melanocytes and melanoma cells to induced pluripotent stem cell (iPSCs) to investigate the relationship between cellular plasticity and melanoma progression and mitogen-activated protein kinase (MAPK) inhibitor resistance. We found that melanocyte reprogramming is prevented by the expression of oncogenic BRAF, and in melanoma cells harboring oncogenic BRAF and sensitive to MAPK inhibitors, reprogramming can be restored by inhibition of the activated oncogenic pathway. Our data also suggest that melanoma tumor progression acts as a barrier to reprogramming. Under conditions that promote melanocytic differentiation of fibroblast- and melanocyte-derived iPSCs, melanoma-derived iPSCs exhibited neural cell-like dysplasia and increased MAPK inhibitor resistance. These data suggest that iPSC-like reprogramming and drug resistance of differentiated cells can serve as a model to understand melanoma cell plasticity-dependent mechanisms in recurrence of aggressive drug-resistant melanoma.

Castro-P’erez, E., Rodr’iguez, C.I., Mikheil, D., Siddique, S., McCarthy, A., Newton, M.A., and , Setaluri. Melanoma Progression Inhibits Pluripotency and Differentiation of Melanoma-Derived iPSCs Produces Cells with Neural-like Mixed Dysplastic Phenotype. 23327. 2019 Stem Cell Reports (13):1.

Concepts Keywords
BRAF IPSCs melanoma
Drug Resistance Tumor
Dysplasia Melanocytes melanoma
Fibroblast Branches of biology
Inhibitor Stem cells
Kinase Cancer
MAPK Melanoma
Melanocyte RTT
Melanocytes BRAF
Melanoma Melanocyte
Mitogen Oncogene
Oncogenic Induced stem cells
Phenotype Binimetinib
Phenotypic Plasticity
Plasticity
Pluripotency
Pluripotent
Tumor

Semantics

Type Source Name
disease MESH recurrence
disease MESH tumor
pathway BSID Melanoma
disease DOID Melanoma
disease MESH Melanoma

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