RNA-seq Characterization of Melanoma Phenotype Switch in 3D Collagen after p38 MAPK Inhibitor Treatment

• Published in: Biomolecules (Basel, Switzerland) Vol. 11; no. 3; p. 449
• Main Authors: Čermák, Vladimír, Škarková, Aneta, Merta, Ladislav, Kolomazníková, Veronika, Palušová, Veronika, Uldrijan, Stjepan, Rösel, Daniel, Brábek, Jan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.03.2021; MDPI
• Subjects: amoeboid invasion; cancer; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Proliferation - genetics; Collagen; Collagen - metabolism; Communication; Experiments; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic - drug effects; Gene Ontology; Genotype & phenotype; Humans; Imidazoles - pharmacology; Kinases; Localization; MAP kinase; Medical prognosis; Melanoma; Melanoma - genetics; Melanoma - pathology; Mesenchyme; Metastases; Metastasis; Microenvironments; Morphology; Naphthalenes - pharmacology; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Phenotype; phenotype switch; Phenotypes; Phenotypic plasticity; Principal components analysis; Protein Kinase Inhibitors - pharmacology; Pyrazoles - pharmacology; Pyridines - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; RNA-Seq - methods; Transcriptomes; Transcriptomics; Tumor microenvironment; Tumor Microenvironment - drug effects; Tumor Microenvironment - genetics; Tumors; United States > US; melanoma; cancer; amoeboid invasion; metastasis; phenotype switch
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom11030449

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.