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.

• Klíčová slova
• amoeboid invasion, cancer, melanoma, metastasis, phenotype switch,
• MeSH
• buněčná diferenciace účinky léků   genetika   MeSH
• fenotyp MeSH
• genová ontologie MeSH
• imidazoly farmakologie   MeSH
• inhibitory proteinkinas farmakologie   MeSH
• kolagen metabolismus   MeSH
• lidé MeSH
• melanom genetika   patologie   MeSH
• mitogenem aktivované proteinkinasy p38 antagonisté a inhibitory   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorové mikroprostředí účinky léků   genetika   MeSH
• naftaleny farmakologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proliferace buněk účinky léků   genetika   MeSH
• pyrazoly farmakologie   MeSH
• pyridiny farmakologie   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• sekvenování transkriptomu metody   MeSH
• stanovení celkové genové exprese metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole MeSH Prohlížeč
• doramapimod MeSH Prohlížeč
• imidazoly MeSH
• inhibitory proteinkinas MeSH
• kolagen MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• naftaleny MeSH
• pyrazoly MeSH
• pyridiny MeSH

The incidence of cutaneous malignant melanoma (CMM) is significantly increasing worldwide.[...].

• Klíčová slova
• BRAF V600 mutation, advanced therapy of melanoma, melanoma, therapeutic resistance,
• Publikační typ
• úvodníky MeSH