Journal
BIOMOLECULES
Volume 11, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/biom11030449
Keywords
cancer; melanoma; metastasis; phenotype switch; amoeboid invasion
Categories
Funding
- Kellner Family Foundation Principal Investigator Grant
- Centre for Tumour Ecology - Operational Programme Research, Development and Education [CZ.02.1.01/0.0/0.0/16_019/0000785]
- Ministry of Education, Youth and Sports of CR within the National Sustainability Program II (Project BIOCEV-FAR) [LQ1604]
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This study shows that phenotype plasticity in melanoma can be induced by treatment with p38 MAPK inhibitors, leading to a switch from a more dedifferentiated invasive phenotype to a more differentiated state. This phenotypic change is accompanied by alterations in gene expression and morphological transition, contributing to invasion and metastasis in melanoma.
Melanoma phenotype plasticity underlies tumour dissemination and resistance to therapy, yet its regulation is incompletely understood. In vivo switching between a more differentiated, proliferative phenotype and a dedifferentiated, invasive phenotype is directed by the tumour microenvironment. We found that treatment of partially dedifferentiated, invasive A375M2 cells with two structurally unrelated p38 MAPK inhibitors, SB2021920 and BIRB796, induces a phenotype switch in 3D collagen, as documented by increased expression of melanocyte differentiation markers and a loss of invasive phenotype markers. The phenotype is accompanied by morphological change corresponding to amoeboid-mesenchymal transition. We performed RNA sequencing with an Illumina HiSeq platform to fully characterise transcriptome changes underlying the switch. Gene expression results obtained with RNA-seq were validated by comparing them with RT-qPCR. Transcriptomic data generated in the study will extend the present understanding of phenotype plasticity in melanoma and its contribution to invasion and metastasis.
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